1
|
Liu Z, Sun Y, Li Y, Ma A, Willaims NF, Jahanbahkshi S, Hoyd R, Wang X, Zhang S, Zhu J, Xu D, Spakowicz D, Ma Q, Liu B. An Explainable Graph Neural Framework to Identify Cancer-Associated Intratumoral Microbial Communities. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2403393. [PMID: 39225619 PMCID: PMC11538693 DOI: 10.1002/advs.202403393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Revised: 06/26/2024] [Indexed: 09/04/2024]
Abstract
Microbes are extensively present among various cancer tissues and play critical roles in carcinogenesis and treatment responses. However, the underlying relationships between intratumoral microbes and tumors remain poorly understood. Here, a MIcrobial Cancer-association Analysis using a Heterogeneous graph transformer (MICAH) to identify intratumoral cancer-associated microbial communities is presented. MICAH integrates metabolic and phylogenetic relationships among microbes into a heterogeneous graph representation. It uses a graph transformer to holistically capture relationships between intratumoral microbes and cancer tissues, which improves the explainability of the associations between identified microbial communities and cancers. MICAH is applied to intratumoral bacterial data across 5 cancer types and 5 fungi datasets, and its generalizability and reproducibility are demonstrated. After experimentally testing a representative observation using a mouse model of tumor-microbe-immune interactions, a result consistent with MICAH's identified relationship is observed. Source tracking analysis reveals that the primary known contributor to a cancer-associated microbial community is the organs affected by the type of cancer. Overall, this graph neural network framework refines the number of microbes that can be used for follow-up experimental validation from thousands to tens, thereby helping to accelerate the understanding of the relationship between tumors and intratumoral microbiomes.
Collapse
Affiliation(s)
- Zhaoqian Liu
- School of MathematicsShandong UniversityJinanShandong250100China
- College of SciencesXi'an University of Science and TechnologyXi'anShanxi710054China
| | - Yuhan Sun
- School of MathematicsShandong UniversityJinanShandong250100China
| | - Yingjie Li
- Department of Biomedical InformaticsThe Ohio State UniversityColumbusOH43210USA
| | - Anjun Ma
- Department of Biomedical InformaticsThe Ohio State UniversityColumbusOH43210USA
- Pelotonia Institute for Immuno‐OncologyThe Ohio State UniversityColumbusOH43210USA
| | - Nyelia F. Willaims
- Department of Internal MedicineCollege of MedicineThe Ohio State UniversityColumbusOH43210USA
| | - Shiva Jahanbahkshi
- Department of Food Science and TechnologyCollege of FoodAgricultural, and Environmental SciencesThe Ohio State UniversityColumbusOH43210USA
| | - Rebecca Hoyd
- Department of Internal MedicineCollege of MedicineThe Ohio State UniversityColumbusOH43210USA
| | - Xiaoying Wang
- Department of Biomedical InformaticsThe Ohio State UniversityColumbusOH43210USA
- Pelotonia Institute for Immuno‐OncologyThe Ohio State UniversityColumbusOH43210USA
| | - Shiqi Zhang
- Department of Human SciencesCollege of Education and Human EcologyThe Ohio State UniversityColumbusOH43210USA
| | - Jiangjiang Zhu
- Department of Human SciencesCollege of Education and Human EcologyThe Ohio State UniversityColumbusOH43210USA
| | - Dong Xu
- Department of Electrical Engineering and Computer ScienceUniversity of MissouriColumbiaMO65201USA
- Christopher S. Bond Life Sciences CenterUniversity of MissouriColumbiaMO65201USA
| | - Daniel Spakowicz
- Pelotonia Institute for Immuno‐OncologyThe Ohio State UniversityColumbusOH43210USA
- Department of Internal MedicineCollege of MedicineThe Ohio State UniversityColumbusOH43210USA
| | - Qin Ma
- Department of Biomedical InformaticsThe Ohio State UniversityColumbusOH43210USA
- Pelotonia Institute for Immuno‐OncologyThe Ohio State UniversityColumbusOH43210USA
| | - Bingqiang Liu
- School of MathematicsShandong UniversityJinanShandong250100China
- Shandong National Center for Applied MathematicsJinanShandong250199China
| |
Collapse
|
2
|
Millapán T, Gutiérrez Á, Rosas K, Buchegger K, Ili CG, Brebi P. In Silico Insights Reveal Fibronectin 1 as a Theranostic Marker in Gastric Cancer. Int J Mol Sci 2024; 25:11113. [PMID: 39456895 PMCID: PMC11507984 DOI: 10.3390/ijms252011113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Revised: 10/09/2024] [Accepted: 10/10/2024] [Indexed: 10/28/2024] Open
Abstract
Gastric cancer (GC) is a complex and highly variable disease, ranking among the top five cancers diagnosed globally, and a leading cause of cancer-related deaths. Emerging from stomach lining cells amid chronic inflammation, it often advances to preneoplastic stages. Late-stage diagnoses and treatment challenges highlight the critical need for early detection and innovative biomarkers, motivating this study's focus on identifying theranostic markers through gene ontology analysis. By exploring deregulated biological processes, this study aims to uncover insights into cancer progression and associated markers, potentially identifying novel theranostic candidates in GC. Using public data from The Human Protein Atlas, this study pinpointed 299 prognostic genes, delineating 171 with unfavorable prognosis and 128 with favorable prognosis. Functional enrichment and protein-protein interaction analyses, supported by RNAseq results and conducted via Metascape and Cytoscape, highlighted five genes (vWF, FN1, THBS1, PCDH7, and F5) with promising theranostic potential. Notably, FN1 and THBS1 exhibited significant promise, with FN1 showing a 370% expression increase in cancerous tissue, and it is possible that FN1 can also indicate the stratification status in GC. While further validation is essential, these findings provide new insights into molecular alterations in GC and potential avenues for clinical application of theranostic markers.
Collapse
Affiliation(s)
- Tatiana Millapán
- Laboratory of Integrative Biology (LIBi), Centro de Excelencia en Medicina Traslacional (CEMT), Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco 4810296, Chile; (T.M.)
- Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile
| | - Álvaro Gutiérrez
- Laboratory of Integrative Biology (LIBi), Centro de Excelencia en Medicina Traslacional (CEMT), Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco 4810296, Chile; (T.M.)
- Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile
- Doctoral Program in Sciences with a Specialization in Applied Cellular and Molecular Biology, Universidad de La Frontera, Temuco 4810296, Chile
| | - Krisnna Rosas
- Laboratory of Integrative Biology (LIBi), Centro de Excelencia en Medicina Traslacional (CEMT), Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco 4810296, Chile; (T.M.)
- Biotechnology Engineering Program, Universidad de La Frontera, Temuco 4810296, Chile
| | - Kurt Buchegger
- Laboratory of Integrative Biology (LIBi), Centro de Excelencia en Medicina Traslacional (CEMT), Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco 4810296, Chile; (T.M.)
- Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile
- BMRC, Biomedical Research Consortium, Santiago 8331150, Chile
- Department of Basic Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4810296, Chile
| | - Carmen Gloria Ili
- Laboratory of Integrative Biology (LIBi), Centro de Excelencia en Medicina Traslacional (CEMT), Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco 4810296, Chile; (T.M.)
- Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile
- BMRC, Biomedical Research Consortium, Santiago 8331150, Chile
| | - Priscilla Brebi
- Laboratory of Integrative Biology (LIBi), Centro de Excelencia en Medicina Traslacional (CEMT), Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco 4810296, Chile; (T.M.)
- Millennium Institute on Immunology and Immunotherapy, Santiago 8331150, Chile
- BMRC, Biomedical Research Consortium, Santiago 8331150, Chile
| |
Collapse
|
3
|
Magalhães-Gama F, Malheiros Araújo Silvestrini M, Neves JCF, Araújo ND, Alves-Hanna FS, Kerr MWA, Carvalho MPSS, Tarragô AM, Soares Pontes G, Martins-Filho OA, Malheiro A, Teixeira-Carvalho A, Costa AG. Exploring cell-derived extracellular vesicles in peripheral blood and bone marrow of B-cell acute lymphoblastic leukemia pediatric patients: proof-of-concept study. Front Immunol 2024; 15:1421036. [PMID: 39234258 PMCID: PMC11371606 DOI: 10.3389/fimmu.2024.1421036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Accepted: 07/25/2024] [Indexed: 09/06/2024] Open
Abstract
Extracellular vesicles (EVs) are heterogeneous, phospholipid membrane enclosed particles that are secreted by healthy and cancerous cells. EVs are present in diverse biological fluids and have been associated with the severity of diseases, which indicates their potential as biomarkers for diagnosis, prognosis and as therapeutic targets. This study investigated the phenotypic characteristics of EVs derived from peripheral blood (PB) and bone marrow (BM) in pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) during different treatment stages. PB and BM plasma were collected from 20 B-ALL patients at three time points during induction therapy, referred to as: diagnosis baseline (D0), day 15 of induction therapy (D15) and the end of the induction therapy (D35). In addition, PB samples were collected from 10 healthy children at a single time point. The EVs were measured using CytoFLEX S flow cytometer. Calibration beads were employed to ensure accurate size analysis. The following, fluorescent-labeled specific cellular markers were used to label the EVs: Annexin V (phosphatidylserine), CD235a (erythrocyte), CD41a (platelet), CD51 (endothelial cell), CD45 (leukocyte), CD66b (neutrophil), CD14 (monocyte), CD3 (T lymphocyte), CD19, CD34 and CD10 (B lymphoblast/leukemic blast). Our results demonstrate that B-ALL patients had a marked production of EV-CD51/61+, EV-CD10+, EV-CD19+ and EV-CD10+CD19+ (double-positive) with a decrease in EV-CD41a+ on D0. However, the kinetics and signature of production during induction therapy revealed a clear decline in EV-CD10+ and EV-CD19+, with an increase of EV-CD41a+ on D35. Furthermore, B-ALL patients showed a complex biological network, exhibiting distinct profiles on D0 and D35. Interestingly, fold change and ROC curve analysis demonstrated that EV-CD10+CD19+ were associated with B-ALL patients, exhibited excellent clinical performance and standing out as a potential diagnostic biomarker. In conclusion, our data indicate that EVs represent a promising field of investigation in B-ALL, offering the possibility of identifying potential biomarkers and therapeutic targets.
Collapse
Affiliation(s)
- Fábio Magalhães-Gama
- Programa de Pós-graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-graduação em Ciências da Saúde, Instituto René Rachou - Fundação Oswaldo Cruz (FIOCRUZ) Minas, Belo Horizonte, Brazil
- Grupo Integrado de Pesquisas em Biomarcadores, Belo Horizonte, Brazil
| | - Marina Malheiros Araújo Silvestrini
- Programa de Pós-graduação em Ciências da Saúde, Instituto René Rachou - Fundação Oswaldo Cruz (FIOCRUZ) Minas, Belo Horizonte, Brazil
- Grupo Integrado de Pesquisas em Biomarcadores, Belo Horizonte, Brazil
| | - Juliana Costa Ferreira Neves
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
| | - Nilberto Dias Araújo
- Programa de Pós-graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-graduação em Ciências Aplicadas à Hematologia, UEA, Manaus, Brazil
| | - Fabíola Silva Alves-Hanna
- Programa de Pós-graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
| | - Marlon Wendell Athaydes Kerr
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-graduação em Ciências Aplicadas à Hematologia, UEA, Manaus, Brazil
| | - Maria Perpétuo Socorro Sampaio Carvalho
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-graduação em Ciências Aplicadas à Hematologia, UEA, Manaus, Brazil
| | - Andréa Monteiro Tarragô
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-graduação em Ciências Aplicadas à Hematologia, UEA, Manaus, Brazil
| | - Gemilson Soares Pontes
- Programa de Pós-graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
- Programa de Pós-graduação em Ciências Aplicadas à Hematologia, UEA, Manaus, Brazil
- Laboratório de Virologia e Imunologia, Instituto Nacional de Pesquisas da Amazônia (INPA), Manaus, Brazil
| | - Olindo Assis Martins-Filho
- Programa de Pós-graduação em Ciências da Saúde, Instituto René Rachou - Fundação Oswaldo Cruz (FIOCRUZ) Minas, Belo Horizonte, Brazil
- Grupo Integrado de Pesquisas em Biomarcadores, Belo Horizonte, Brazil
- Programa de Pós-graduação em Ciências Aplicadas à Hematologia, UEA, Manaus, Brazil
| | - Adriana Malheiro
- Programa de Pós-graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-graduação em Ciências Aplicadas à Hematologia, UEA, Manaus, Brazil
| | - Andréa Teixeira-Carvalho
- Programa de Pós-graduação em Ciências da Saúde, Instituto René Rachou - Fundação Oswaldo Cruz (FIOCRUZ) Minas, Belo Horizonte, Brazil
- Grupo Integrado de Pesquisas em Biomarcadores, Belo Horizonte, Brazil
- Programa de Pós-graduação em Ciências Aplicadas à Hematologia, UEA, Manaus, Brazil
| | - Allyson Guimarães Costa
- Programa de Pós-graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-graduação em Ciências Aplicadas à Hematologia, UEA, Manaus, Brazil
| |
Collapse
|
4
|
Shirai Y, Hamura R, Tanji Y, Taniai T, Yanagaki M, Haruki K, Furukawa K, Onda S, Sakamoto T, Gocho T, Ikegami T. The postoperative platelet-to-lymphocyte ratio predicts the outcome of patients undergoing pancreaticoduodenectomy for pancreatic head cancer. Surg Today 2024; 54:247-257. [PMID: 37488354 DOI: 10.1007/s00595-023-02727-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Accepted: 06/22/2023] [Indexed: 07/26/2023]
Abstract
PURPOSE The preoperative platelet-to-lymphocyte ratio (PLR) has been reported as an important prognostic index for pancreatic ductal adenocarcinoma (PDAC); however, the significance of the postoperative (post-op) PLR for this disease has not been elucidated. METHODS We analyzed data on 118 patients who underwent pancreaticoduodenectomy for pancreatic head PDAC, collected from a prospectively maintained database. The post-op PLR was obtained by dividing the platelet count after surgery by the lymphocyte count on post-op day (POD) 14. The patients were divided into two groups according to a post-op PLR of < 310 or ≥ 310. Survival data were analyzed. RESULTS A high post-op PLR was identified as a significant prognostic index on univariate analysis for disease-free survival (DFS) and overall survival (OS). The post-op PLR remained significant, along with tumor differentiation and adjuvant chemotherapy, on multivariate analysis for OS (hazard ratio = 2.077, 95% confidence interval: 1.220-3.537; p = 0.007). The post-op PLR was a significant independent prognostic index for poor DFS, along with tumor differentiation and lymphatic invasion, on multivariate analysis (hazard ratio = 1.678, 95% confidence interval: 1.056-2.667; p = 0.028). CONCLUSIONS The post-op PLR in patients with pancreatic head PDAC was an independent predictor of DFS and OS after elective resection.
Collapse
Affiliation(s)
- Yoshihiro Shirai
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan.
- Department of Gastrointestinal Surgery, Saku General Hospital Advanced Care Center, Nagano, 385-0051, Japan.
| | - Ryoga Hamura
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
- Department of Gastrointestinal Surgery, Saku General Hospital Advanced Care Center, Nagano, 385-0051, Japan
| | - Yoshiaki Tanji
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
| | - Tomohiko Taniai
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
| | - Mitsuru Yanagaki
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
| | - Koichiro Haruki
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
| | - Kenei Furukawa
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
| | - Shinji Onda
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
- Department of Gastrointestinal Surgery, Saku General Hospital Advanced Care Center, Nagano, 385-0051, Japan
| | - Taro Sakamoto
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
| | - Takeshi Gocho
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
| | - Toru Ikegami
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, The Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-Ku, Tokyo, 105-8461, Japan
| |
Collapse
|
5
|
Dong H, Huang Z, Yang D, Li Z, Huang H, Meng Z, Qin Y, Kang M. Prognostic value of EBV DNA and platelet-to-lymphocyte ratio in patients with non-metastatic nasopharyngeal carcinoma: a retrospective study. BMC Cancer 2023; 23:673. [PMID: 37464319 DOI: 10.1186/s12885-023-11117-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 06/27/2023] [Indexed: 07/20/2023] Open
Abstract
PURPOSE Analyzing the prognostic value of Epstein-Barr virus (EBV) DNA load and platelet-to-lymphocyte ratio (PLR) in non-metastatic nasopharyngeal carcinoma (NPC) patients, thereby developing a reliable and effective marker. METHODS We compared survival rates among different groups using the Kaplan-Meier method and the Log-rank test. The factors affecting the prognosis of NPC patients were determined using univariate and multivariate cox regression analysis. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. RESULTS The ROC curve indicated a cut-off value of 775 copies/ml for EBV DNA and 203.3 for PLR. Kaplan-Meier and Log-rank tests showed that 3-year overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) of NPC patients in high risk group (HRG) were significantly poorer than those in medium risk group (MRG) and low risk group (LRG). The 3-year OS of NPC patients was significantly correlated with age, N stage and EBV DNA-PLR. The 3-year LRFS were significantly correlated with sex, N stage, histology type, and EBV DNA-PLR. The 3-year DMFS were correlated with histology type. The ROC curve showed that area under the curve (AUC) values of EBV DNA-PLR of 3-year OS, LRFS and DMFS in NPC were higher than those of PLR and EBV DNA. CONCLUSION EBV DNA-PLR is an independent risk factor for the prognosis of NPC. Compared with PLR or EBV DNA alone, the combination of EBV DNA and PLR may be more accurate in predicting the prognosis of NPC patients.
Collapse
Affiliation(s)
- Huan Dong
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China
- Department of Radiotherapy and Chemotherapy, The Second People's Hospital of Yichang, No. 21, Xiling 1st Road, Yichang, Hubei, 443000, People's Republic of China
| | - Zichong Huang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China
- Department of Oncology, Langdong Hospital of Guangxi Medical University, No. 60, Jinhu North Road, Nanning, Guangxi, 530028, People's Republic of China
| | - Dong Yang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China
| | - Zhiru Li
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China
| | - Heqing Huang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China
| | - Zhen Meng
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China
| | - Yutao Qin
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China.
| | - Min Kang
- Department of Radiation Oncology, The First Affiliated Hospital of Guangxi Medical University, No. 6, Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China.
| |
Collapse
|
6
|
Magalhães-Gama F, Alves-Hanna FS, Araújo ND, Barros MS, Silva FS, Catão CLS, Moraes JS, Freitas IC, Tarragô AM, Malheiro A, Teixeira-Carvalho A, Costa AG. The Yin-Yang of myeloid cells in the leukemic microenvironment: Immunological role and clinical implications. Front Immunol 2022; 13:1071188. [PMID: 36532078 PMCID: PMC9751477 DOI: 10.3389/fimmu.2022.1071188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Accepted: 11/14/2022] [Indexed: 12/02/2022] Open
Abstract
The leukemic microenvironment has a high diversity of immune cells that are phenotypically and functionally distinct. However, our understanding of the biology, immunology, and clinical implications underlying these cells remains poorly investigated. Among the resident immune cells that can infiltrate the leukemic microenvironment are myeloid cells, which correspond to a heterogeneous cell group of the innate immune system. They encompass populations of neutrophils, macrophages, and myeloid-derived suppressor cells (MDSCs). These cells can be abundant in different tissues and, in the leukemic microenvironment, are associated with the clinical outcome of the patient, acting dichotomously to contribute to leukemic progression or stimulate antitumor immune responses. In this review, we detail the current evidence and the many mechanisms that indicate that the activation of different myeloid cell populations may contribute to immunosuppression, survival, or metastatic dissemination, as well as in immunosurveillance and stimulation of specific cytotoxic responses. Furthermore, we broadly discuss the interactions of tumor-associated neutrophils and macrophages (TANs and TAMs, respectively) and MDSCs in the leukemic microenvironment. Finally, we provide new perspectives on the potential of myeloid cell subpopulations as predictive biomarkers of therapeutical response, as well as potential targets in the chemoimmunotherapy of leukemias due to their dual Yin-Yang roles in leukemia.
Collapse
Affiliation(s)
- Fábio Magalhães-Gama
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-Graduação em Ciências da Saúde, Instituto René Rachou - Fundação Oswaldo Cruz (FIOCRUZ) Minas, Belo Horizonte, Brazil
- Grupo Integrado de Pesquisas em Biomarcadores de Diagnóstico e Monitoração, Instituto René Rachou – FIOCRUZ Minas, Belo Horizonte, Brazil
| | - Fabíola Silva Alves-Hanna
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
| | - Nilberto Dias Araújo
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
| | - Mateus Souza Barros
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
| | - Flavio Souza Silva
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
| | - Claudio Lucas Santos Catão
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
| | - Júlia Santos Moraes
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
| | - Izabela Cabral Freitas
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
| | - Andréa Monteiro Tarragô
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
- Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
| | - Adriana Malheiro
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
- Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
| | - Andréa Teixeira-Carvalho
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-Graduação em Ciências da Saúde, Instituto René Rachou - Fundação Oswaldo Cruz (FIOCRUZ) Minas, Belo Horizonte, Brazil
- Grupo Integrado de Pesquisas em Biomarcadores de Diagnóstico e Monitoração, Instituto René Rachou – FIOCRUZ Minas, Belo Horizonte, Brazil
| | - Allyson Guimarães Costa
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Programa de Pós-Graduação em Ciências da Saúde, Instituto René Rachou - Fundação Oswaldo Cruz (FIOCRUZ) Minas, Belo Horizonte, Brazil
- Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
- Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Escola de Enfermagem de Manaus, UFAM, Manaus, Brazil
| |
Collapse
|
7
|
Banna GL, Friedlaender A, Tagliamento M, Mollica V, Cortellini A, Rebuzzi SE, Prelaj A, Naqash AR, Auclin E, Garetto L, Mezquita L, Addeo A. Biological Rationale for Peripheral Blood Cell-Derived Inflammatory Indices and Related Prognostic Scores in Patients with Advanced Non-Small-Cell Lung Cancer. Curr Oncol Rep 2022; 24:1851-1862. [PMID: 36255605 DOI: 10.1007/s11912-022-01335-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/16/2022] [Indexed: 01/27/2023]
Abstract
PURPOSE OF REVIEW To describe the biological rationale of peripheral blood cells (PBC)-derived inflammatory indexes and assess the related prognostic scores for patients with advanced non-small cell lung cancer (aNSCLC) treated with immune-checkpoint inhibitors (ICI). RECENT FINDINGS Inflammatory indexes based on PBC may indicate a pro-inflammatory condition affecting the immune response to cancer. The lung immune prognostic index (LIPI), consisting of derived neutrophils-to-lymphocyte ratio (NLR) and lactate dehydrogenase, is a validated prognostic tool, especially for pretreated aNSCLC patients, where the combination of NLR and PD-L1 tumour expression might also be predictive of immunotherapy benefit. In untreated high-PD-L1 aNSCLC patients, the Lung-Immune-Prognostic score (LIPS), including NLR, ECOG PS and concomitant steroids, is prognostic, and its modified version might indicate patients with favourable outcomes despite an ECOG PS of 2. NLR times platelets (i.e., SII), included in the NHS-Lung score, might improve the prognostication for combined chemoimmunotherapy. PBC-derived inflammatory indexes and related scores represent accurate, reproducible and non-expensive prognostic tools with clinical and research utility.
Collapse
Affiliation(s)
| | - Alex Friedlaender
- Department of Oncology, Clinique Générale Beaulieu, Geneva, Switzerland
- Department of Oncology, University Hospital of Geneva, Geneva, Switzerland
| | - Marco Tagliamento
- Department of Internal Medicine and Medical Specialties (Di.M.I.), University of Genoa, Genoa, Italy
| | - Veronica Mollica
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138, Bologna, Italy
| | - Alessio Cortellini
- Division of Cancer, Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK
| | - Sara Elena Rebuzzi
- Department of Internal Medicine and Medical Specialties (Di.M.I.), University of Genoa, Genoa, Italy
- Medical Oncology Unit, Ospedale San Paolo, Savona, Italy
| | - Arsela Prelaj
- Medical Oncology Department 1, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
- Department of Electronics, Information, and Bioengineering, Politecnico di Milano, Milan, Italy
| | - Abdul Rafeh Naqash
- Medical Oncology/TSET Phase 1 Program, Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK, USA
| | - Edouard Auclin
- Medical Oncology, Hôpital Européen Georges Pompidou, AP-HP, Université Paris Cité, Paris, France
| | - Lucia Garetto
- Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Turin, Italy
| | - Laura Mezquita
- Medical Oncology Department, Hospital Clinic of Barcelona, Barcelona, Spain
- Laboratory of Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, Spain
- Department of Medicine, University of Barcelona, Barcelona, Spain
| | - Alfredo Addeo
- Department of Oncology, University Hospital of Geneva, Geneva, Switzerland
| |
Collapse
|
8
|
Gharahkhani R, Pourhadi M, Mirdamadi NS, Dana N, Rafiee L, Nedaeinia R, Javanmard SH. Effect of Anti-Podoplanin on Malignant Glioma Cell Viability, Invasion and Tumor Cell-Induced Platelet Aggregation. Arch Med Res 2022; 53:461-468. [DOI: 10.1016/j.arcmed.2022.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 02/05/2022] [Accepted: 05/06/2022] [Indexed: 11/02/2022]
|
9
|
Kucuk A, Topkan E, Selek U, Haksoyler V, Mertsoylu H, Besen AA, Pehlivan B. High Measures of Pre-Chemoradiotherapy Platelet-to-Albumin Ratio Indicates Poor Prognosis in Locally Advanced Pancreatic Cancer Patients. Ther Clin Risk Manag 2022; 18:421-428. [PMID: 35444422 PMCID: PMC9015102 DOI: 10.2147/tcrm.s359553] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Accepted: 04/03/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose In a lack of similar research, we meant to retrospectively investigate the prognostic significance of pre-chemoradiotherapy (C-CRT) platelet-to-albumin ratio (PAR) on the survival results of locally advanced unresectable pancreatic adenocarcinoma (LAPC) patients. Patients and Methods The present analysis included 139 LAPC patients who received C-CRT in total. The utility of pre-C-CRT cutoff(s) reshaping survival data was explored using receiver operating characteristic (ROC) curve analysis. The primary and secondary objectives were the associations between PAR levels and overall survival (OS) and progression-free survival (PFS) outcomes. Results At a median follow-up of 15.7 months (95% CI: 11.6–19.8), the overall cohort’s median and 5-year OS rates were 14.4 months (95% CI: 11.8–17) and 14.7%, respectively, while the corresponding PFS rates were 7.8 months (95% CI: 6.5–9.1) and 11.2%. Because the ROC curve analysis found 4.9 as the optimal PAR cutoff for both OS and PFS [area under the curve (AUC): 75.4%; sensitivity: 72.4%; specificity: 70.3%], we divided the patients into two PAR cohorts: PAR<4.9 (N=60) and PAR≥4.9 (N=79). Comparative analysis per PAR group exhibited significantly worse OS (11.2 vs 18.6 months, and 9.8% vs 20.9% at 5 years, P=0.003) and DFS (7 vs 14.3 months, and 7.6% vs 16.2% at 5 years, P=0.001) with PAR≥4.9 versus PAR<4.9, respectively. In multivariate analysis, the N0 nodal status, CA 19–9≤90 U/mL, and PAR<4.9 were found to be independent predictors of improved OS and PFS. Conclusion The pre-C-CRT high PAR (≥4.9) robustly and independently prognosticated significantly worse OS and PFS results in inoperable LAPC patients who underwent definitive C-CRT.
Collapse
Affiliation(s)
- Ahmet Kucuk
- Clinic of Radiation Oncology, Mersin Education and Research Hospital, Mersin, Turkey
| | - Erkan Topkan
- Department of Radiation Oncology, Baskent University Medical Faculty, Adana, Turkey
- Correspondence: Erkan Topkan, Department of Radiation Oncology, Baskent University Medical Faculty, Adana, Turkey, Tel +90-533-7381069, Fax +90-322-3444452, Email
| | - Ugur Selek
- Department of Radiation Oncology, Koc University School of Medicine, Istanbul, Turkey
- Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | | | - Huseyin Mertsoylu
- Department of Medical Oncology, Baskent University Medical Faculty, Adana, Turkey
| | - Ali Ayberk Besen
- Department of Medical Oncology, Baskent University Medical Faculty, Adana, Turkey
| | - Berrin Pehlivan
- Department of Radiation Oncology, Bahcesehir University, Istanbul, Turkey
| |
Collapse
|
10
|
Menter DG, Afshar-Kharghan V, Shen JP, Martch SL, Maitra A, Kopetz S, Honn KV, Sood AK. Of vascular defense, hemostasis, cancer, and platelet biology: an evolutionary perspective. Cancer Metastasis Rev 2022; 41:147-172. [PMID: 35022962 PMCID: PMC8754476 DOI: 10.1007/s10555-022-10019-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 01/04/2022] [Indexed: 01/08/2023]
Abstract
We have established considerable expertise in studying the role of platelets in cancer biology. From this expertise, we were keen to recognize the numerous venous-, arterial-, microvascular-, and macrovascular thrombotic events and immunologic disorders are caused by severe, acute-respiratory-syndrome coronavirus 2 (SARS-CoV-2) infections. With this offering, we explore the evolutionary connections that place platelets at the center of hemostasis, immunity, and adaptive phylogeny. Coevolutionary changes have also occurred in vertebrate viruses and their vertebrate hosts that reflect their respective evolutionary interactions. As mammals adapted from aquatic to terrestrial life and the heavy blood loss associated with placentalization-based live birth, platelets evolved phylogenetically from thrombocytes toward higher megakaryocyte-blebbing-based production rates and the lack of nuclei. With no nuclei and robust RNA synthesis, this adaptation may have influenced viral replication to become less efficient after virus particles are engulfed. Human platelets express numerous receptors that bind viral particles, which developed from archetypal origins to initiate aggregation and exocytic-release of thrombo-, immuno-, angiogenic-, growth-, and repair-stimulatory granule contents. Whether by direct, evolutionary, selective pressure, or not, these responses may help to contain virus spread, attract immune cells for eradication, and stimulate angiogenesis, growth, and wound repair after viral damage. Because mammalian and marsupial platelets became smaller and more plate-like their biophysical properties improved in function, which facilitated distribution near vessel walls in fluid-shear fields. This adaptation increased the probability that platelets could then interact with and engulf shedding virus particles. Platelets also generate circulating microvesicles that increase membrane surface-area encounters and mark viral targets. In order to match virus-production rates, billions of platelets are generated and turned over per day to continually provide active defenses and adaptation to suppress the spectrum of evolving threats like SARS-CoV-2.
Collapse
Affiliation(s)
- David G Menter
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| | - Vahid Afshar-Kharghan
- Division of Internal Medicine, Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| | - John Paul Shen
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Stephanie L Martch
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Anirban Maitra
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Scott Kopetz
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kenneth V Honn
- Department of Pathology, Bioactive Lipids Research Program, Wayne State University, 5101 Cass Ave. 430 Chemistry, Detroit, MI, 48202, USA
- Department of Pathology, Wayne State University School of Medicine, 431 Chemistry Bldg, Detroit, MI, 48202, USA
- Cancer Biology Division, Wayne State University School of Medicine, 431 Chemistry Bldg, Detroit, MI, 48202, USA
| | - Anil K Sood
- Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
- Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
- Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA
| |
Collapse
|
11
|
Kim HJ, Lee KH, Shim HJ, Hwang EC, Choi YD, Bang H, Cho SH, Chung IJ, Hwang JE, Lee MA, Bae WK. Prognostic Significance of the Neutrophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio in Neuroendocrine Carcinoma. Chonnam Med J 2022; 58:29-36. [PMID: 35169557 PMCID: PMC8813653 DOI: 10.4068/cmj.2022.58.1.29] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 11/23/2021] [Accepted: 11/24/2021] [Indexed: 11/25/2022] Open
Abstract
Extra-pulmonary neuroendocrine carcinoma is a rare and aggressive cancer. Although several biological and histological markers have been suggested as prognostic factors for this cancer, the prognostic importance of systemic inflammatory markers, including the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, is unclear. This study aimed to evaluate the association between systemic inflammatory markers and the prognosis of extra-pulmonary neuroendocrine carcinoma. We retrospectively analyzed the clinical data of 85 patients with unresectable or metastatic extra-pulmonary neuroendocrine carcinoma who received platinum-based chemotherapy as first-line chemotherapy from August 2007 to November 2019. We used time-dependent receiver operating characteristic curve analysis to determine the cut-off values. The cut-off values for the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were 3.0 and 158.5, respectively. There was no significant difference in the Eastern Cooperative Oncology Group performance status score, Ki-67 index, or response to chemotherapy between groups. The high neutrophil-lymphocyte ratio group showed significantly worse overall survival (high vs. low, median 11.1 vs. 21.0 months, log-rank p=0.004) and shorter median progression-free survival, but the latter was not statistically significant. The high platelet-lymphocyte ratio group also showed significantly worse progression-free survival and overall survival than the low platelet-lymphocyte ratio group (high vs. low: median 5.6 vs. 9.8 months, log-rank p=0.047 and median 13.8 vs. 21.0 months, log-rank p=0.013, respectively). In multivariable analysis, a high neutrophil-lymphocyte ratio was an independent prognostic factor for overall survival. The neutrophil-lymphocyte ratio is a potent and readily available prognostic factor for extra-pulmonary neuroendocrine carcinoma.
Collapse
Affiliation(s)
- Hyeon-Jong Kim
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Kang Han Lee
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Hyun Jeong Shim
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Eu Chang Hwang
- Department of Urology, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Yoo-Duk Choi
- Department of Pathology, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Hyunjin Bang
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Sang Hee Cho
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Ik-Joo Chung
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
- Immunotherapy Innovation Center, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Jun Eul Hwang
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| | - Myung Ah Lee
- Division of Medical Oncology, Department of Internal Medicine, Cancer Research Institute, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea
| | - Woo Kyun Bae
- Division of Hematology-Oncology, Department of Internal Medicine, Chonnam National University Medical School and Hwasun Hospital, Hwasun, Korea
| |
Collapse
|
12
|
Jia W, Yuan L, Ni H, Xu B, Zhao P. Prognostic Value of Platelet-to-Lymphocyte Ratio, Neutrophil-to-Lymphocyte Ratio, and Lymphocyte-to-White Blood Cell Ratio in Colorectal Cancer Patients Who Received Neoadjuvant Chemotherapy. Technol Cancer Res Treat 2021; 20:15330338211034291. [PMID: 34308689 PMCID: PMC8317245 DOI: 10.1177/15330338211034291] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Background: The objective of this study was to assess the prognostic value of pretreatment platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-white blood cell ratio (LWR) of CRC patients who received neoadjuvant chemotherapy. Methods: We analyzed the peripheral blood routine parameters and other clinical data of 145 patients with colorectal cancer who had undergone neoadjuvant chemotherapy between January 2011 and February 2014. Pretreatment blood parameters of 145 patients were collected, and PLR, NLR, and LWR were calculated. The utility of PLR, NLR, and LWR in predicting treatment efficacy and patient survival was statistically evaluated using the chi-square test, log-rank test, Kaplan-Meier curves and logistic regression models, and Cox regression models. Results: Receiver operating characteristic curve showed that the best cutoff values of PLR, NLR, and LWR were 154.31, 3.01, and 0.22, respectively. In univariate analysis, tumor location (P = 0.044), differentiation degree (P = 0.001), lymph node metastasis (P = 0.020), and high PLR (P = 0.042) were significantly correlated with a lower overall response rate (ORR). In addition, clinical stage, lymph node metastasis, and high PLR were correlated with short OS (P < 0.01) and DFS (P < 0.01). Moreover, WBC count was correlated with a short OS. Multivariate analysis showed that tumor location (P = 0.013), differentiation degree (P = 0.001), and lymph node metastasis (P = 0.033) were independent predictors of ORR. In addition, lymph node metastasis independently predicted a shorter OS (P = 0.011). Lymph node metastasis (P = 0.013) and high PLR (P = 0.022) were independent prognostic factors for short DFS. Conclusions: For CRC patients who received NAC, clinical pathological stage and lymph node metastasis were correlated with lower ORR and survival, while a high PLR that may be of prognostic relevance in CRC patients receiving NAC.
Collapse
Affiliation(s)
- Wangqiang Jia
- Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, People's Republic of China
| | - Long Yuan
- Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, People's Republic of China
| | - Hongyan Ni
- Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, People's Republic of China
| | - Benling Xu
- Department of Immunotherapy, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, People's Republic of China
| | - Peng Zhao
- Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan, People's Republic of China
| |
Collapse
|
13
|
Batur AF, Aydogan MF, Kilic O, Korez MK, Gul M, Kaynar M, Goktas S, Akand M. Comparison of De Ritis Ratio and other systemic inflammatory parameters for the prediction of prognosis of patients with transitional cell bladder cancer. Int J Clin Pract 2021; 75:e13743. [PMID: 32991771 DOI: 10.1111/ijcp.13743] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2020] [Revised: 09/13/2020] [Accepted: 09/23/2020] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVE To investigate the clinical value of preoperative De Ritis ratio (aspartate aminotransferase/alanine aminotransferase) (DRR) in patients with transitional cell bladder cancer (TCBC) at initial diagnosis. The secondary objective was to investigate the status of systemic inflammatory parameters, such as neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR) and platelet-monocyte ratio (PMR). MATERIALS AND METHODS The records of patients with primary TCBC who underwent transurethral resection were retrospectively evaluated. The relationship of DRR and systemic inflammatory parameters with clinicopathological findings, recurrence and progression status was evaluated separately. RESULTS There was no significant difference in the DRR according to the clinicopathological findings, recurrence and progression. Significant differences were found between the NLR and the patient groups for tumour diameter, tumour stage, tumour grade and progression. In univariate analysis, the LMR was found to be associated with progression, and also the PLR and LMR were found to be associated with recurrence. Decrease in LMR and increase in LMR score demonstrated by multiple analysis was shown as independent predictors of progression and recurrence development. CONCLUSIONS This paper shows a positive correlation between poor prognosis in TCBC and the systemic inflammatory markers, namely NLR, LMR, PLR and PMR, but not DRR.
Collapse
Affiliation(s)
- Ali Furkan Batur
- Department of Urology, Selcuk University School of Medicine, Konya, Turkey
| | | | - Ozcan Kilic
- Department of Urology, Selcuk University School of Medicine, Konya, Turkey
| | - Muslu Kazım Korez
- Department of Biostatistics, Selcuk University School of Medicine, Konya, Turkey
| | - Murat Gul
- Department of Urology, Selcuk University School of Medicine, Konya, Turkey
| | - Mehmet Kaynar
- Department of Urology, Selcuk University School of Medicine, Konya, Turkey
| | - Serdar Goktas
- Department of Urology, Selcuk University School of Medicine, Konya, Turkey
| | - Murat Akand
- Department of Urology, Selcuk University School of Medicine, Konya, Turkey
| |
Collapse
|
14
|
Wang J, Zhou P, Han Y, Zhang H. Platelet transfusion for cancer secondary thrombocytopenia: Platelet and cancer cell interaction. Transl Oncol 2021; 14:101022. [PMID: 33545547 PMCID: PMC7868729 DOI: 10.1016/j.tranon.2021.101022] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 01/13/2021] [Accepted: 01/14/2021] [Indexed: 01/14/2023] Open
Abstract
Chemoradiotherapy and autoimmune disorder often lead to secondary thrombocytopenia in cancer patients, and thus, platelet transfusion is needed to stop or prevent bleeding. However, the effect of platelet transfusion remains controversial for the lack of agreement on transfusion strategies. Before being transfused, platelets are stored in blood banks, and their activation is usually stimulated. Increasing evidence shows activated platelets may promote metastasis and the proliferation of cancer cells, while cancer cells also induce platelet activation. Such a vicious cycle of interaction between activated platelets and cancer cells is harmful for the prognosis of cancer patients, which results in an increased tumor recurrence rate and decreased five-year survival rate. Therefore, it is important to explore platelet transfusion strategies, summarize mechanisms of interaction between platelets and tumor cells, and carefully evaluate the pros and cons of platelet transfusion for better treatment and prognosis for patients with cancer with secondary thrombocytopenia.
Collapse
Affiliation(s)
- Juan Wang
- Class 2016 Clinical Medicine, Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Pan Zhou
- Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Yunwei Han
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China.
| | - Hongwei Zhang
- Department of Blood Transfusion, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China.
| |
Collapse
|
15
|
Schmied L, Höglund P, Meinke S. Platelet-Mediated Protection of Cancer Cells From Immune Surveillance - Possible Implications for Cancer Immunotherapy. Front Immunol 2021; 12:640578. [PMID: 33777033 PMCID: PMC7988080 DOI: 10.3389/fimmu.2021.640578] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 02/09/2021] [Indexed: 12/19/2022] Open
Abstract
The growing insights in the complex interactions between metastatic cancer-cells and platelets have revealed that platelet tumor cell interactions in the blood stream are an important factor supporting tumor metastasis. An increased coagulability of platelets facilitates the vascular evasion and establishment of solid tumor metastasis. Furthermore, platelets can support an immunosuppressive tumor microenvironment or shield tumor cells directly from engagement of cytotoxic lymphocytes as e.g., natural killer (NK) cells. Platelets are both in the tumor microenvironment and systemically the quantitatively most important source of TGF-β, which is a key cytokine for immunosuppression in the tumor microenvironment. If similar platelet-tumor interactions are of physiological relevance in hematological malignancies remains less well-studied. This might be important, as T- and NK cell mediated graft vs. leukemia effects (GvL) are well-documented and malignant hematological cells have a high exposure to platelets compared to solid tumors. As NK cell-based immunotherapies gain increasing attention as a therapeutic option for patients suffering from hematological and other malignancies, we review the known interactions between platelets and NK cells in the solid tumor setting and discuss how these could also apply to hematological cancers. We furthermore explore the possible implications for NK cell therapy in patients with solid tumors and patients who depend on frequent platelet transfusions. As platelets have a protective and supportive effect on cancer cells, the impact of platelet transfusion on immunotherapy and the combination of immunotherapy with platelet inhibitors needs to be evaluated.
Collapse
Affiliation(s)
- Laurent Schmied
- Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Huddinge, Sweden
| | - Petter Höglund
- Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Huddinge, Sweden
| | - Stephan Meinke
- Department of Medicine Huddinge, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Huddinge, Sweden
| |
Collapse
|
16
|
Zanetto A, Senzolo M, Campello E, Bulato C, Gavasso S, Shalaby S, Gambato M, Vitale A, Cillo U, Farinati F, Russo FP, Simioni P, Burra P. Influence of Hepatocellular Carcinoma on Platelet Aggregation in Cirrhosis. Cancers (Basel) 2021; 13:cancers13051150. [PMID: 33800224 PMCID: PMC7962527 DOI: 10.3390/cancers13051150] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 02/23/2021] [Accepted: 03/01/2021] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Platelets are blood cells, the main function of which is to form clots and prevent/stop bleeding. However, it has been shown that platelets may be involved in additional pathophysiological processes, including stimulation of cancer growth and metastasis. In fact, inhibition of platelets in patients with various types of cancer has resulted in lower risks of cancer progression and death. This possibility has not yet been considered in patients with cirrhosis (chronic liver disease) and hepatocellular carcinoma (the most common type of liver cancer) because their platelet function has never been investigated. In this study, we show that hepatocellular carcinoma in patients with cirrhosis is associated with significantly altered (increased) platelet function. This paves the way for further studies to evaluate whether the inhibition of these hyper-functional platelets could be beneficial in patients with cirrhosis and hepatocellular carcinoma. Abstract Hyper-functional platelets are being proposed as a potential therapeutic target in multiple cancers. Whether this can be considered in patients with cirrhosis and hepatocellular carcinoma (HCC) is unknown as their platelet function has not yet been investigated. We evaluated platelet function in cirrhosis patients with HCC. Patients with cirrhosis with and without HCC were prospectively recruited. Platelet aggregation, a marker of platelet function, was assessed by impedance aggregometry with adenosine diphosphate (ADP), arachidonic acid (ASPI), and thrombin (TRAP) stimulation. Plasmatic levels of Von Willebrand factor antigen (VWF) were also determined. One-hundred patients were recruited (50 cirrhotics with and 50 without HCC). Cirrhosis severity by Child class and platelet count were comparable between cirrhotics with and without HCC. Cirrhotics with HCC had higher ADP- (45 vs. 28; p < 0.001), ASPI- (47 vs. 28; p < 0.001), and TRAP- (85 vs. 75; p = 0.01) induced platelet aggregation than cirrhotics without HCC, all indicative of platelet hyper-function. The relatively increased platelet aggregation in patients with HCC was confirmed after adjusting the analysis for platelet count/severity of thrombocytopenia. Levels of VWF were higher in patients with vs. without HCC (348 vs. 267; p = 0.006), particularly in compensated cirrhosis. In patients with cirrhosis, HCC is associated with increased platelet aggregation and higher VWF. The clinical implications of these findings deserve further investigation.
Collapse
Affiliation(s)
- Alberto Zanetto
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy; (A.Z.); (M.S.); (S.S.); (F.F.); (F.P.R.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy;
| | - Marco Senzolo
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy; (A.Z.); (M.S.); (S.S.); (F.F.); (F.P.R.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy;
| | - Elena Campello
- Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, 35128 Padova, Italy; (E.C.); (C.B.); (S.G.)
| | - Cristiana Bulato
- Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, 35128 Padova, Italy; (E.C.); (C.B.); (S.G.)
| | - Sabrina Gavasso
- Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, 35128 Padova, Italy; (E.C.); (C.B.); (S.G.)
| | - Sarah Shalaby
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy; (A.Z.); (M.S.); (S.S.); (F.F.); (F.P.R.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy;
| | - Martina Gambato
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy;
| | - Alessandro Vitale
- Hepatobiliary Surgery and Liver Transplantation Center, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy; (A.V.); (U.C.)
| | - Umberto Cillo
- Hepatobiliary Surgery and Liver Transplantation Center, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy; (A.V.); (U.C.)
| | - Fabio Farinati
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy; (A.Z.); (M.S.); (S.S.); (F.F.); (F.P.R.)
| | - Francesco Paolo Russo
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy; (A.Z.); (M.S.); (S.S.); (F.F.); (F.P.R.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy;
| | - Paolo Simioni
- Thrombotic and Hemorrhagic Diseases Unit, General Internal Medicine, Padova University Hospital, 35128 Padova, Italy; (E.C.); (C.B.); (S.G.)
- Correspondence: (P.S.); (P.B.); Tel.: +39-049-8212667 (P.S.); +39-049-8212892 (P.B.)
| | - Patrizia Burra
- Gastroenterology, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy; (A.Z.); (M.S.); (S.S.); (F.F.); (F.P.R.)
- Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, 35128 Padova, Italy;
- Correspondence: (P.S.); (P.B.); Tel.: +39-049-8212667 (P.S.); +39-049-8212892 (P.B.)
| |
Collapse
|
17
|
Giannetta E, La Salvia A, Rizza L, Muscogiuri G, Campione S, Pozza C, Colao AALI, Faggiano A. Are Markers of Systemic Inflammatory Response Useful in the Management of Patients With Neuroendocrine Neoplasms? Front Endocrinol (Lausanne) 2021; 12:672499. [PMID: 34367064 PMCID: PMC8339959 DOI: 10.3389/fendo.2021.672499] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 05/03/2021] [Indexed: 11/13/2022] Open
Abstract
Given the increasing incidence of neuroendocrine neoplasms (NENs) over the past few decades, a more comprehensive knowledge of their pathophysiological bases and the identification of innovative NEN biomarkers represents an urgent unmet need. There is still little advance in the early diagnosis and management of these tumors, due to the lack of sensible and specific markers with prognostic value and ability to early detect the response to treatment. Chronic systemic inflammation is a predisposing factor for multiple cancer hallmarks, as cancer proliferation, progression and immune-evading. Therefore, the relevance of inflammatory biomarkers has been identified as critical in several types of tumours, including NENs. A bidirectional relationship between chronic inflammation and development of NENs has been reported. Neuroendocrine cells can be over-stimulated by chronic inflammation, leading to hyperplasia and neoplastic transformation. As the modulation of inflammatory response represents a therapeutic target, inflammatory markers could represent a promising new key tool to be applied in the diagnosis, the prediction of response to treatment and also as prognostic biomarkers in NENs field. The present review provides an overview of the pre-clinical and clinical data relating the potentially usefulness of circulating inflammatory markers: neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), cytokines and tissue inflammatory markers (PD-1/PD-L1), in the management of NENs. (1) NLR and PLR have both demonstrated to be promising and simple to acquire biomarkers in patients with advanced cancer, including NEN. To date, in the context of NENs, the prognostic role of NLR and PLR has been confirmed in 15 and 4 studies, respectively. However, the threshold value, both for NLR and PLR, still remains not defined. (2) Cytokines seem to play a central role in NENs tumorigenesis. In particular, IL-8 levels seems to be a good predictive marker of response to anti-angiogenic treatments. (3) PD-1 and PD-L1 expression on tumour cells and on TILs, have demonstrated to be promising predictive and prognostic biomarkers in NENs. Unfortunately, these two markers have not been validated so far and further studies are needed to establish their indications and utility.
Collapse
Affiliation(s)
- Elisa Giannetta
- Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy
- *Correspondence: Elisa Giannetta,
| | - Anna La Salvia
- Department of Oncology, University Hospital 12 de Octubre, Madrid, Spain
| | - Laura Rizza
- Endocrinology Unit, Department of Oncology and Medical Specialities, AO San Camillo-Forlanini, Rome, Italy
| | - Giovanna Muscogiuri
- Endocrinology Unit Department of Clinical Medicine and Surgery, University Federico II School of Medicine, Naples, Italy
| | - Severo Campione
- A. Cardarelli Hospital, Naples Department of Advanced Diagnostic-Therapeutic Technologies and Health Services Section of Anatomic Pathology, Naples, Italy
| | - Carlotta Pozza
- Department of Experimental Medicine, “Sapienza” University of Rome, Rome, Italy
| | | | - Antongiulio Faggiano
- Department of Clinical and Molecular Medicine, Endocrine-Metabolic Unit, Sant’Andrea University Hospital “Sapienza” University of Rome, Rome, Italy
| |
Collapse
|
18
|
Li TC, Wang LL, Liu BL, Hong JJ, Xu NN, Tang K, Zheng XW. Association between bone marrow fluorodeoxyglucose uptake and recurrence after curative surgical resection in patients with T1-2N0M0 lung adenocarcinoma: a retrospective cohort study. Quant Imaging Med Surg 2020; 10:2285-2296. [PMID: 33269227 DOI: 10.21037/qims-19-962] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Background Evidence regarding the relationship between fluorodeoxyglucose (FDG) uptake in the bone marrow of patients with lung adenocarcinoma and prognosis is limited. This study aimed to identify whether bone marrow FDG uptake is a risk factor for recurrence in patients after curative surgical resection of T1-2N0M0 lung adenocarcinoma. Methods From January 2012 to December 2016, we retrospectively enrolled 195 pT1-2N0M0 lung adenocarcinoma patients who underwent both preoperative FDG positron emission tomography/computed tomography (PET/CT) and surgical resection from the lung adenocarcinoma database maintained by the PET/CT department at our hospital. After surgical resection, patients were followed up mainly through regular outpatient examinations. The maximum standardized uptake value (SUVmax) of the primary tumor, the mean FDG uptake of bone marrow (BM SUV), bone marrow-liver uptake ratio (BLR), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured from the pretreatment FDG PET/CT images. Multi-adjusted Cox proportional hazards models were built to evaluate the independent prognostic value of BLR in predicting recurrence-free survival (RFS). A restricted cubic spline regression model was conducted to provide more precise estimates and examine the shape of the associations between BLR and the risk of recurrence. Results The follow-up results showed that 30 of the 195 patients (15.4%) had tumor recurrence. Compared with non-recurrent patients, the primary tumor size in recurrent patients was larger, and the SUVmax, TLG, and serum C-reactive protein (CRP) levels were higher. Univariate analysis showed that BLR, tumor size, SUVmax, TLG, and CRP were significantly correlated with postoperative tumor recurrence. After adjustment for conventional confounding factors, the hazard ratio of BLR was 5.01 (95% CI, 1.32, 18.98) for the highest tertile of BLR compared with the lowest tertile. The multi-adjusted spline regression showed that BLR had a linear relationship with log relative risk (RR) for recurrence when BLR was lower than 0.7. Over this level, the effect stabilized, suggesting a saturation effect for BLR at a level of approximately 0.7 at recurrence. Conclusions BLR was an independent risk factor for predicting RFS in T1-2N0M0 lung adenocarcinoma patients after curative surgical resection. BLR can be used as a biomarker for evaluating the risk of lung cancer recurrence.
Collapse
Affiliation(s)
- Tian-Cheng Li
- PET Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Li-Li Wang
- Department of PET/CT, Radiology Imaging Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Bo-Le Liu
- Department of PET/CT, Radiology Imaging Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jun-Jie Hong
- Department of PET/CT, Radiology Imaging Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ni-Na Xu
- Department of PET/CT, Radiology Imaging Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Kun Tang
- Department of PET/CT, Radiology Imaging Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xiang-Wu Zheng
- Department of PET/CT, Radiology Imaging Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| |
Collapse
|
19
|
Asghar S, Waqar W, Umar M, Manzoor S. Tumor educated platelets, a promising source for early detection of hepatocellular carcinoma: Liquid biopsy an alternative approach to tissue biopsy. Clin Res Hepatol Gastroenterol 2020; 44:836-844. [PMID: 32312598 DOI: 10.1016/j.clinre.2020.03.023] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Revised: 03/17/2020] [Accepted: 03/23/2020] [Indexed: 02/05/2023]
Abstract
PURPOSE Liver cancer is considered to be the sixth deadliest cancer worldwide. Hepatocellular carcinoma (HCC) is known to be the most prevalent type of liver cancer. The number of deaths due to HCC reported per year is on a constant rise especially in lesser developed countries. There are several contributing factors to this rise in number. Among other contributing factors is the late diagnosis of HCC. Patients are usually diagnosed when the disease reaches its advance stage. The present study was conducted with total 30 samples. It was designed for investigating the potential of TGF-β, NF-κβ, VEGF, AKT and PI3K as RNA based biomarkers in tumor educated platelets for early detection of HCC. RESULTS The results obtained from the transcriptional analysis revealed a significant high expression of TGF-β, NF-κβ, VEGF by 2.48, 2.35 and 2.78 folds respectively in comparison to the control. On the other hand, a decrease in expression by 0.6 and 0.65 folds was observed in AKT and PI3K respectively in comparison to controls. Although all selected RNA biomarkers showed promising potential to detect HCC however, AKT and PI3K were better able to detect early stage HCC. CONCLUSIONS The results obtained clearly indicate the increased expression of TGF-β, NF-κβ, VEGF in HCC patients. All these biomarkers are previously known for cancer initiation, progression and metastasis. The significant decrease in expression of AKT and PI3K in HCC patients needs further investigation. All the selected RNA biomarkers can be used for detection of HCC as they were able to distinguish HCC patients from controls successfully with AKT and PI3K showing better potential to detect early stage HCC. However, translational analysis for all these RNA biomarkers should be performed to gain further evidence for the ability of these biomarkers to be used for early HCC detection.
Collapse
Affiliation(s)
- Sidra Asghar
- Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, H12, 44000 Islamabad, Pakistan.
| | - Walifa Waqar
- Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, H12, 44000 Islamabad, Pakistan.
| | - Muhammad Umar
- Centre for Liver and Digestive Diseases Holy Family Hospital, Rawalpindi, Pakistan.
| | - Sobia Manzoor
- Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, H12, 44000 Islamabad, Pakistan.
| |
Collapse
|
20
|
Biswas T, Kang KH, Gawdi R, Bajor D, Machtay M, Jindal C, Efird JT. Using the Systemic Immune-Inflammation Index (SII) as a Mid-Treatment Marker for Survival among Patients with Stage-III Locally Advanced Non-Small Cell Lung Cancer (NSCLC). INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:E7995. [PMID: 33143164 PMCID: PMC7662688 DOI: 10.3390/ijerph17217995] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 10/20/2020] [Accepted: 10/23/2020] [Indexed: 02/06/2023]
Abstract
The Systemic Immune-Inflammation Index (SII) is an important marker of immune function, defined as the product of neutrophil-to-lymphocyte ratio (NLR) and platelet count (P). Higher baseline SII levels have been associated with improved survival in various types of cancers, including lung cancer. Data were obtained from PROCLAIM, a randomized phase III trial comparing two different chemotherapy regimens pemetrexed + cisplatin (PEM) vs. etoposide + cisplatin (ETO), in combination with radiotherapy (RT) for the treatment of stage III non-squamous non-small cell lung cancer (NSCLC). We aimed to determine if SII measured at the mid-treatment window for RT (weeks 3-4) is a significant predictor of survival, and if the effect of PEM vs. ETO differs by quartile (Q) level of SII. Hazard-ratios (HR) for survival were estimated using a proportional hazards model, accounting for the underlying correlated structure of the data. A total of 548 patients were included in our analysis. The median age at baseline was 59 years. Patients were followed for a median of 24 months. Adjusting for age, body mass index, sex, race, and chemotherapy regimen, SII was a significant mid-treatment predictor of both overall (adjusted HR (aHR) = 1.6, p < 0.0001; OS) and progression-free (aHR = 1.3, p = 0.0072; PFS) survival. Among patients with mid-RT SII values above the median (6.8), those receiving PEM (vs. ETO) had superior OS (p = 0.0002) and PFS (p = 0.0002). Our secondary analysis suggests that SII is an informative mid-treatment marker of OS and PFS in locally advanced non-squamous NSCLC.
Collapse
Affiliation(s)
- Tithi Biswas
- Department of Radiation Oncology, University Hospitals, Case Western Reserve University, Cleveland, OH 44106, USA;
| | - Kylie H. Kang
- Department of Radiation Oncology, Washington University School of Medicine and Alvin J. Siteman Comprehensive Cancer Center, St. Louis, MO 63110, USA;
| | - Rohin Gawdi
- Wake Forest School of Medicine, Winston-Salem, NC 27101, USA;
| | - David Bajor
- Medical Oncology, Seidman Cancer Center, Case Western Reserve University, Cleveland, OH 44106, USA;
| | - Mitchell Machtay
- Department of Radiation Oncology, Penn State University, Hershey, PA 17033, USA;
| | - Charu Jindal
- Faculty of Science, University of Newcastle, Newcastle 2308, Australia;
| | - Jimmy T. Efird
- Cooperative Studies Program Epidemiology Center, Health Services Research and Development (DVAHCS/Duke Affiliated Center), Durham, NC 27705, USA
| |
Collapse
|
21
|
Josefsson EC, Vainchenker W, James C. Regulation of Platelet Production and Life Span: Role of Bcl-xL and Potential Implications for Human Platelet Diseases. Int J Mol Sci 2020; 21:ijms21207591. [PMID: 33066573 PMCID: PMC7589436 DOI: 10.3390/ijms21207591] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 10/09/2020] [Accepted: 10/10/2020] [Indexed: 01/14/2023] Open
Abstract
Blood platelets have important roles in haemostasis, where they quickly stop bleeding in response to vascular damage. They have also recognised functions in thrombosis, immunity, antimicrobal defense, cancer growth and metastasis, tumour angiogenesis, lymphangiogenesis, inflammatory diseases, wound healing, liver regeneration and neurodegeneration. Their brief life span in circulation is strictly controlled by intrinsic apoptosis, where the prosurvival Bcl-2 family protein, Bcl-xL, has a major role. Blood platelets are produced by large polyploid precursor cells, megakaryocytes, residing mainly in the bone marrow. Together with Mcl-1, Bcl-xL regulates megakaryocyte survival. This review describes megakaryocyte maturation and survival, platelet production, platelet life span and diseases of abnormal platelet number with a focus on the role of Bcl-xL during these processes.
Collapse
Affiliation(s)
- Emma C Josefsson
- The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC 3052, Australia
- Department of Medical Biology, University of Melbourne, Melbourne, VIC 3052, Australia
| | - William Vainchenker
- University Paris-Saclay, INSERM UMR 1270, Gustave Roussy, 94800 Villejuif, France
| | - Chloe James
- University of Bordeaux, INSERM U1034, Biology of Cardiovascular Diseases, 33600 Pessac, France
- Laboratory of Hematology, Bordeaux University Hospital Center, Haut-Leveque Hospital, 33604 Pessac, France
| |
Collapse
|
22
|
Fiorica F, Colella M, Taibi R, Bonetti A, Giuliani J, Perrone MS, Missiroli S, Giorgi C. Glioblastoma: Prognostic Factors and Predictive Response to Radio and Chemotherapy. Curr Med Chem 2020; 27:2814-2825. [PMID: 32003678 DOI: 10.2174/0929867327666200131095256] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Revised: 12/01/2019] [Accepted: 12/12/2019] [Indexed: 12/14/2022]
Abstract
Glioblastoma multiforme (GBM) is characterized by poor prognosis despite an aggressive therapeutic strategy. In recent years, many advances have been achieved in the field of glioblastoma biology. Here we try to summarize the main clinical and biological factors impacting clinical prognostication and therapy of GBM patients. From that standpoint, hopefully, in the near future, personalized therapies will be available.
Collapse
Affiliation(s)
- Francesco Fiorica
- Department of Radiation Oncology, AULSS 9 Scaligera, Verona, Italy.,Department of Radiation Oncology, University Hospital Ferrara, Ferrara, Italy
| | - Maria Colella
- Department of Radiation Oncology, University Hospital Ferrara, Ferrara, Italy
| | - Rosaria Taibi
- Department of Medical Oncology, National Cancer Institute, Aviano (PN), Italy
| | - Andrea Bonetti
- Department of Oncology, AULSS 9 Scaligera, Verona, Italy
| | | | - Maria Sole Perrone
- Department of Medical Sciences, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy
| | - Sonia Missiroli
- Department of Medical Sciences, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy
| | - Carlotta Giorgi
- Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy
| |
Collapse
|
23
|
Zhang J, Feng W, Ye Z, Wei Y, Li L, Yang Y. Prognostic significance of platelet-to-lymphocyte ratio in patients with nasopharyngeal carcinoma: a meta-analysis. Future Oncol 2019; 16:117-127. [PMID: 31789058 DOI: 10.2217/fon-2019-0520] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Aim: Several studies reported the association of platelet-to-lymphocyte ratio (PLR) and prognosis in nasopharyngeal carcinoma (NPC), but the results remain controversial. Therefore, we investigated the prognostic value of PLR in NPC through meta-analysis. Materials & methods: A comprehensive literature search of PubMed, Embase and Web of Science was performed. Results: A total of 9 studies comprising of 3459 patients with NPC were included. The data demonstrated that an increased PLR predicted poor overall survival, progression-free survival and distant metastasis-free survival. There was no significant association between PLR and sex, age, T stage, N stage, tumor node metastasis (TNM) stage or intensity-modulated radiotherapy. Conclusion: This meta-analysis revealed that PLR might be a potential predicative biomarker of poor prognosis in patients with NPC.
Collapse
Affiliation(s)
- Junkai Zhang
- Department I of Medical Oncology Center, Zhongshan Hospital of Sun Yat-sen University, People's Hospital of Zhongshan City, Zhongshan, Guangdong 528403, PR China
| | - Weineng Feng
- Department of Head & Neck/Thoracic Medical Oncology, The First People's Hospital of Foshan, Foshan, Guangdong 528000, PR China
| | - Zhihua Ye
- Department I of Medical Oncology Center, Zhongshan Hospital of Sun Yat-sen University, People's Hospital of Zhongshan City, Zhongshan, Guangdong 528403, PR China
| | - Ying Wei
- Department I of Medical Oncology Center, Zhongshan Hospital of Sun Yat-sen University, People's Hospital of Zhongshan City, Zhongshan, Guangdong 528403, PR China
| | - Lamei Li
- Department I of Medical Oncology Center, Zhongshan Hospital of Sun Yat-sen University, People's Hospital of Zhongshan City, Zhongshan, Guangdong 528403, PR China
| | - Yingyu Yang
- Department I of Medical Oncology Center, Zhongshan Hospital of Sun Yat-sen University, People's Hospital of Zhongshan City, Zhongshan, Guangdong 528403, PR China
| |
Collapse
|
24
|
Liu L, Song X, Li X, Xue L, Ding S, Niu L, Xie L, Song X. A three-platelet mRNA set: MAX, MTURN and HLA-B as biomarker for lung cancer. J Cancer Res Clin Oncol 2019; 145:2713-2723. [PMID: 31552488 DOI: 10.1007/s00432-019-03032-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 09/18/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND During the development of tumors, tumors "educate" platelets causing changes in their mRNAs expression profiles and phenotypes, thereby, tumor-educated platelet (TEP) mRNA profile has the potential to diagnose lung cancer. The current study aimed to examine whether TEPs might be a potential biomarker for lung cancer diagnostics. METHODS Platelet precipitation was obtained by low-speed centrifugation and subjected to Trizol for total RNA extraction. Platelet MAX, MTURN, and HLA-B mRNA were selected by microarray, validated by qPCR, and analyzed combined with related clinical factors. RESULTS Our results showed that a three-platelet mRNA set: MAX, MTURN, and HLA-B was significantly up-regulated in lung cancer patients as well as in early-stage lung cancer patients compared with those from healthy donors, the area under the curve (AUC) was 0.734, 0.787, respectively, among which platelet MTURN mRNA processed a dramatically high diagnostic efficiency in female patients with lung cancer, its AUC for female was 0.825. More importantly, the three-platelet mRNA set: MAX, MTURN, and HLA-B was associated with chemotherapeutic effect, low mRNA expression of this three-platelet set was correlated with "favorable" first chemotherapy response. CONCLUSIONS A three-platelet mRNA set: MAX, MTURN and HLA-B enables blood-based lung cancer diagnosis and chemotherapy response prediction.
Collapse
Affiliation(s)
- Lele Liu
- School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, Jinan, China
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Xingguo Song
- Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Xinyi Li
- School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, Jinan, China
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Linlin Xue
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Shanshan Ding
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
- Department of Clinical Laboratory, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China
| | - Limin Niu
- School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences, Jinan, China
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Li Xie
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Xianrang Song
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
| |
Collapse
|
25
|
Ikuta S, Sonoda T, Aihara T, Yamanaka N. A combination of platelet-to-lymphocyte ratio and carbohydrate antigen 19-9 predict early recurrence after resection of pancreatic ductal adenocarcinoma. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:461. [PMID: 31700897 DOI: 10.21037/atm.2019.08.35] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Background Early recurrence (ER) after surgical resection is an important factor that impacts the survival of patients with pancreatic ductal adenocarcinoma (PDA). We examined risk factors for ER after PDA resection. Methods One hundred and thirteen PDA patients who underwent R0 or R1 resection were retrospectively analyzed. Thirty-four patients (30.1%) received neoadjuvant chemotherapy (NAC) for borderline resectable (BR) (n=13) or initially unresectable (n=21) disease. ER was defined as that diagnosed within 6 months after surgery. Receiver operating characteristic analysis was performed for each variable to determine the optimal cutoff value. Results ER occurred in 21 patients (18.6%). In univariate analysis, preoperative platelet-to-lymphocyte ratio (PLR) ≥144, carbohydrate antigen (CA) 19-9 ≥162 U/mL, and pathological tumor size ≥3 cm were significantly associated with ER. High PLR and CA19-9 were independent risk factors for ER by multivariate analysis. Area under the curve (AUC) for predicting ER from a combination of PLR and CA19-9 was 0.765 (95% confidence interval: 0.664-0.866), which increased the AUC compared to that for each risk factor alone. Patients with both risk factors had a significantly worse overall survival than those with one or no risk factors. When 24 patients with BR-PDA were considered, NAC was associated with a reduced likelihood of having risk factors and with a low ER rate. Conclusions A combination of PLR and CA19-9 is a useful predictor of ER after macroscopic curative resection for PDA. NAC may reduce the risk of ER in selected patients.
Collapse
Affiliation(s)
- Shinichi Ikuta
- Department of Surgery, Meiwa Hospital, Nishinomiya, Hyogo, Japan
| | - Takashi Sonoda
- Department of Medical Oncology, Meiwa Hospital, Nishinomiya, Hyogo, Japan
| | - Tsukasa Aihara
- Department of Surgery, Meiwa Hospital, Nishinomiya, Hyogo, Japan
| | - Naoki Yamanaka
- Department of Surgery, Meiwa Hospital, Nishinomiya, Hyogo, Japan
| |
Collapse
|
26
|
Wang X, Ni X, Tang G. Prognostic Role of Platelet-to-Lymphocyte Ratio in Patients With Bladder Cancer: A Meta-Analysis. Front Oncol 2019; 9:757. [PMID: 31475109 PMCID: PMC6703229 DOI: 10.3389/fonc.2019.00757] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 07/29/2019] [Indexed: 12/24/2022] Open
Abstract
Background: Many studies have been reported that platelet-to-lymphocyte ratio (PLR) may be associated with the prognosis of bladder cancer, but the results are inconsistent. Therefore, we performed a meta-analysis to evaluate the effect of pretreatment PLR on the prognosis of bladder cancer. Methods: The databases PubMed, Embase, Cochrane Library, and Web of Science were searched. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to analyze the relationship between PLR and prognosis. Pooled odds ratios (ORs) and 95% CIs were used to analyze the relationship between PLR and clinicopathological features. Publication bias was estimated using Begg's funnel plot asymmetry tests. Results: A total of 8 studies comprising 3,303 patients were included in this meta-analysis. An elevated PLR was significantly associated with poorer overall survival (OS) (HR = 1.26, 95% CI = 1.03–1.54, p = 0.026), but not with cancer-specific survival (CSS) (HR = 1.15, 95% CI = 0.95–1.38, p = 0.149), or recurrence-free survival (RFS) (HR = 1.72, 95% CI = 0.79–3.75, p = 0.175). In addition, high PLR was correlated with age ≥ 65 years (OR = 1.82, 95% CI = 1.24–2.67, p = 0.002), whereas was not significantly correlated with sex, tumor grade, tumor stage, distant metastasis, or tumor size. Conclusions: The pretreatment PLR could serve as a predicative biomarker of poor prognosis for patients with bladder cancer.
Collapse
Affiliation(s)
- Xingmu Wang
- Center of Clinical Laboratory, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China
| | - Xiaoyan Ni
- Center of Clinical Laboratory, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China
| | - Guiliang Tang
- Department of Urology, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, China
| |
Collapse
|
27
|
Cheng YQ, Wang K, Zhang XP, Wei XB, Jiang YB, Hu YR, Mao FF, Guo WX, Shi J, Cheng SQ. Thrombocytopenia: A prognostic factor for hepatocellular carcinoma patients with portal vein tumor thrombus after hepatectomy. J Gastroenterol Hepatol 2019; 34:1214-1221. [PMID: 30402968 DOI: 10.1111/jgh.14537] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2018] [Revised: 10/23/2018] [Accepted: 10/29/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Portal vein tumor thrombus (PVTT) predicts a poor prognosis in hepatocellular carcinoma (HCC) patients. Platelets (PLTs) play an important role in HCC progression and metastasis. However, the relationship between PLTs and PVTT remains unclear. This study aimed to evaluate the value of PLT counts in the prognosis of HCC patients with PVTT after hepatectomy. METHODS From January 2002 to December 2012, 694 HCC patients with PVTT after hepatectomy were evaluated. The patients were divided into the thrombocytopenia group (PLT < 100 × 109 /L), the normal group, and the thrombocytosis group (PLT > 300 × 109 /L) based on the preoperative PLT level. A propensity score matching (PSM) analysis was used. RESULTS Before the PSM, PVTT patients with thrombocytopenia exhibited longer recurrence-free survival (RFS) and overall survival (OS) compared with those with normal PLT counts (both P < 0.001) or thrombocytosis (P = 0.008 and P = 0.046). For the thrombocytopenia group and the normal group, the 1-, 2-, and 3-year RFS values were 30.0%, 17.6%, and 15.7% and were 10.8%, 6.6%, and 5.8% (P < 0.001), respectively; the 1-, 2-, and 3-year OS values were 61.9%, 37.9%, and 31.2% and were 38.3%, 23.3%, and 16.0% (P < 0.001), respectively. After the PSM, the median survival time was 16.6 versus 8.6 months (P < 0.002) in the two groups. A subgroup analysis revealed that thrombocytopenia is associated with improved OS in those with type I PVTT (P = 0.021) or type II PVTT (P = 0.029). CONCLUSION According to the PSM, preoperative thrombocytopenia predicts an increased RFS and OS in HCC patients with PVTT after hepatectomy.
Collapse
Affiliation(s)
- Yu-Qiang Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Kang Wang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xiu-Ping Zhang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Xu-Biao Wei
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Ya-Bo Jiang
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Yi-Ren Hu
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Fei-Fei Mao
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Wei-Xing Guo
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Jie Shi
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Shu-Qun Cheng
- Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| |
Collapse
|
28
|
Qi Y, Liao D, Fu X, Gao Q, Zhang Y. Elevated platelet-to-lymphocyte corresponds with poor outcome in patients with advanced cancer receiving anti-PD-1 therapy. Int Immunopharmacol 2019; 74:105707. [PMID: 31272066 DOI: 10.1016/j.intimp.2019.105707] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 06/12/2019] [Accepted: 06/14/2019] [Indexed: 12/29/2022]
Abstract
OBJECTIVES The purpose of this retrospective analysis was to investigate the prognostic value of PLR for PD-1 inhibitors. METHODS Patients were divided into different subgroups according to PLR. Univariate survival analysis and a multivariate Cox proportional hazards regression model were used to assess the association between PLR and overall survival (OS) or progression-free survival (PFS). RESULTS The optimal cut-off value of baseline PLR was 164. Among the total 85 patients, 34 patients presented with PLR ≥ 164, and 51 presented with PLR < 164, respectively. The median OS for the high PLR group was 7.0 months (95% CI: 4.1-9.9 months), and it was not reached for the low PLR group (P < 0.001). The median PFS was 3.0 months (95% CI: 1.9-4.1 months) vs. 9.8 months (95% CI: 6.1-13.5 months) for the high and low PLR groups, respectively (P < 0.001). In multivariate analysis, a PLR > 164 and body mass index (BMI) > 24.0 were independently associated with OS (hazard ratio [HR]: 3.549, 95% confidence interval [CI]: 1.901-6.625, P < 0.001 and HR: 0.496, 95% CI: 0.260-0.945, P = 0.033), meanwhile PLR was also significantly associated with inferior PFS (HR: 2.567, 95% CI: 1.551-4.249, P < 0.001). Disease control rate for high and low PLR group was 38.2% and 74.5%, respectively, and it was also correlated with elevated PLR (P = 0.001). CONCLUSION This retrospective analysis indicates that PLR could be used as a biomarker to stratify patients who will have a better response to anti-PD-1 agents.
Collapse
Affiliation(s)
- Yalong Qi
- Department of Biology and Immunotherapy, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, 127 Dong Ming Road, Jin-Shui District, Zhengzhou, Henan 450008, PR China
| | - Daixiang Liao
- Department of Oncology, Beijing Mentougou District Hospital, 10 He Tan Qiao East Road, Mentougou District, Beijing 102300, PR China
| | - Xiaomin Fu
- Department of Biology and Immunotherapy, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, 127 Dong Ming Road, Jin-Shui District, Zhengzhou, Henan 450008, PR China
| | - Quanli Gao
- Department of Biology and Immunotherapy, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, 127 Dong Ming Road, Jin-Shui District, Zhengzhou, Henan 450008, PR China
| | - Yong Zhang
- Department of Biology and Immunotherapy, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, 127 Dong Ming Road, Jin-Shui District, Zhengzhou, Henan 450008, PR China.
| |
Collapse
|
29
|
Combined Diagnostic Efficacy of Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Mean Platelet Volume (MPV) as Biomarkers of Systemic Inflammation in the Diagnosis of Colorectal Cancer. DISEASE MARKERS 2019; 2019:6036979. [PMID: 30800188 PMCID: PMC6360046 DOI: 10.1155/2019/6036979] [Citation(s) in RCA: 104] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2018] [Revised: 11/05/2018] [Accepted: 11/13/2018] [Indexed: 12/14/2022]
Abstract
Background Systemic inflammation in colorectal cancer (CRC) may be reflected by neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV). This study was designed to investigate the efficiency of preoperative NLR, PLR, and MVP as a tool for the assessment of tumor characteristics in newly diagnosed patients with CRC. Patients and Methods For 300 patients and 300 healthy volunteers, complete blood counts with automated differential counts were performed. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count; PLR was calculated by dividing the absolute platelet count by the absolute lymphocyte count. The diagnostic performance of NLR, PLR, and MVP was estimated by ROC curve. Results ROC curve analysis showed high diagnostic efficacy of NLR and PLR in CRC patients with cut-off values of 2.15 (AUC = 0.790, 95% CI 0.736-0.884, Se = 74.1%, and Sp = 73%) and 123 (AUC = 0.846, 95% CI 0.801-0.891, Se = 73.5%, and Sp = 80%) compared to healthy controls, respectively. The diagnostic efficacy of three combined markers was superior compared with individual markers (AUC = 0.904, 95% CI 0.812-0.989, Se = 96%, and Sp = 70%). Conclusion NRL, PLR, and MPV may be useful markers in diagnostic and early recognition of different stages of CRC; additionally combined all together have stronger diagnostic efficacy.
Collapse
|
30
|
Pan YC, Jia ZF, Cao DH, Wu YH, Jiang J, Wen SM, Zhao D, Zhang SL, Cao XY. Preoperative lymphocyte-to-monocyte ratio (LMR) could independently predict overall survival of resectable gastric cancer patients. Medicine (Baltimore) 2018; 97:e13896. [PMID: 30593200 PMCID: PMC6314713 DOI: 10.1097/md.0000000000013896] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Preoperational hemogram parameters have been reported to be associated with the prognosis of several types of cancers. This study aimed to investigate the prognostic value of hematological parameters in gastric cancer in a Chinese population. A total of 870 gastric cancer patients who underwent radical tumorectomy were recruited from January 2008 to December 2012. Preoperative hematological parameters were recorded and dichotomized by time-dependent receiver operating characteristic curves. The survival curves of patients stratified by each hematological parameter were plotted by the Kaplan-Meier method and compared by log-rank test. Multivariate Cox proportional hazards models were used to select parameters independently correlated with prognosis. The median age of the patients was 60 years. The median follow-up time was 59.9 months, and the 5-year survival rate was 56.4%. Results from the univariate analyses showed that low lymphocyte count (<2.05 × 10/L), high neutrophil-to-white blood cell ratio (NWR > 0.55), low lymphocyte-to-white blood cell ratio (LWR < 0.23), low lymphocyte-to-monocyte ratio (LMR < 5.43), high neutrophil-to-lymphocyte ratio (NLR > 1.44), and high platelet-to-lymphocyte ratio (PLR > 115) were associated with poor survival of gastric cancer patients. Multivariate analysis showed that low LMR (HR: 1.49, 95% CI: 1.17-1.89, P = .001) was the only hematological factor independently predicting poor survival. These results indicate that preoperational LMR is an independent prognostic factor for patients with resectable gastric cancer.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | - Xue-Yuan Cao
- Department of Gastrointestinal Surgery, First Hospital of Jilin University, Changchun, China
| |
Collapse
|
31
|
Xue L, Xie L, Song X, Song X. [Expression and Significance of ACIN1 mRNA in Platelets of Lung Cancer]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2018; 21:677-681. [PMID: 30201066 PMCID: PMC6137000 DOI: 10.3779/j.issn.1009-3419.2018.09.05] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND During the occurring and developing of tumor, tumor-educated platelets mRNA profiles were altered. Since platelets are anuclear, the level of mRNAs is probably post-transcriptional regulated by the splicing maturation of pre-mRNA and alternative splicing. Apoptotic chromatin condensation inducer 1 (ACIN1) has been shown to be a component of a splicing-dependent multiprotein exon junction complex (EJC) and was involved in mRNA metabolism associated with splicing. This study analyzed the expression of ACIN1 mRNA in platelets, and explored its potential as a biomarker of lung cancer. METHODS 156 patients with lung cancer and 58 healthy controls in Shandong Cancer Hospital were collected. We isolated platelet pellets by low-speed centrifugation and extracted total RNA. The expression of ACIN1 mRNA in platelets was detected by RT-PCR, the results were analyzed statistically. And the relationship between expression of ACIN1 mRNA and clinical factors were also analyzed. RESULTS The expression level of ACIN1 mRNA in platelets of patients with lung cancer was significantly higher than that in platelets of healthy controls (P=0.015). The ROC curve showed that the area under the curve of ACIN1 mRNA for detecting lung cancer were 0.608. The expression of ACIN1 mRNA in platelets of lung cancer has no significant relationship with age, gender, pathological type and metastasis or not (P>0.05). CONCLUSIONS ACIN1 mRNA was highly expressed in platelets of lung cancer patients, and the detection of its expression level might have potential clinical value for the diagnosis of lung cancer.
Collapse
Affiliation(s)
- Linlin Xue
- Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, China; Shandong Academy of Medical Sciences, Jinan 250002,China
| | - Li Xie
- Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, China; Shandong Academy of Medical Sciences, Jinan 250002,China
| | - Xingguo Song
- Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, China; Shandong Academy of Medical Sciences, Jinan 250002,China
| | - Xianrang Song
- Shandong Cancer Hospital Affiliated to Shandong University, Jinan 250117, China; Shandong Academy of Medical Sciences, Jinan 250002,China
| |
Collapse
|
32
|
Fu X, Zhang Y, Yang J, Qi Y, Ming Y, Sun M, Shang Y, Yang Y, Zhu X, Gao Q. Efficacy and safety of trastuzumab as maintenance or palliative therapy in advanced HER2-positive gastric cancer. Onco Targets Ther 2018; 11:6091-6100. [PMID: 30275713 PMCID: PMC6157990 DOI: 10.2147/ott.s174138] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) is a unique subtype of this disease. Few studies focus on the feasibility of trastuzumab as maintenance or palliative therapy for patients with HER2-positive advanced GC. PATIENTS AND METHODS We retrospectively analyzed the data of 11 patients, evaluated the efficacy and safety of trastuzumab, and attempted to investigate the prognostic factors for trastuzumab treatment. Among the 11 patients, one achieved partial response (PR), six achieved stable disease (SD), and four were evaluated as progressive disease (PD). RESULTS The overall response rate (ORR) was 9.10%, and the disease control rate (DCR) was 63.64%. The median overall survival (OS) was 6.10 months, and the median progression-free survival (PFS) was 6.10 months. A significant association was found between trastuzumab treatment cycles and efficacy (P=0.027), cycles and PFS (P=0.001), and cycles and OS (P=0.005). Among the five patients who accepted more than five cycles of trastuzumab, the median OS and median PFS achieved 23.83 months and 14.67 months, respectively. Moreover, we have found the correlation between tumor marker changes and efficacy (P=0.002) and HER2 status and PFS (P=0.027). No association was found between HER2 status and OS (P=0.597). CONCLUSION The most common adverse events were left ventricular ejection fraction (LVEF) reduction, fatigue, and anorexia. LVEF reduction was found in seven of 11 patients, but the absolute decline in the LVEF was within 10% from the baseline. The results of this study suggest that trastuzumab is a feasible option as maintenance or palliative therapy for patients with HER2-positive metastatic GC.
Collapse
Affiliation(s)
- Xiaomin Fu
- Department of Biology and Immunotherapy, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, People's Republic of China,
| | - Yong Zhang
- Department of Biology and Immunotherapy, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, People's Republic of China,
| | - Jing Yang
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Yalong Qi
- Department of Biology and Immunotherapy, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, People's Republic of China,
| | - Yue Ming
- Department of Biology and Immunotherapy, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, People's Republic of China,
| | - Miaomiao Sun
- Department of Pathology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, People's Republic of China
| | - Yiman Shang
- Department of Biology and Immunotherapy, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, People's Republic of China,
| | - Yonghao Yang
- Department of Biology and Immunotherapy, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, People's Republic of China,
| | - Xiaoyan Zhu
- Department of Histology and Embryology, College of Basic Medicine, Zhengzhou University, Zhengzhou, People's Republic of China,
| | - Quanli Gao
- Department of Biology and Immunotherapy, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, People's Republic of China,
| |
Collapse
|
33
|
Girgin R, Cinar O, Bulut E, Akduman B, Mungan N. The Role of the Platelet Mass Index (PMI) as a New Prognostic Factor in Fournier’s Gangrene. AFRICAN JOURNAL OF UROLOGY 2018. [DOI: 10.1016/j.afju.2018.06.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
|
34
|
Ruytinx P, Proost P, Struyf S. CXCL4 and CXCL4L1 in cancer. Cytokine 2018; 109:65-71. [PMID: 29903575 DOI: 10.1016/j.cyto.2018.02.022] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Revised: 02/16/2018] [Accepted: 02/20/2018] [Indexed: 02/07/2023]
|
35
|
Platelet deficiency in Tpo−/− mice can both promote and suppress the metastasis of experimental breast tumors in an organ-specific manner. Clin Exp Metastasis 2018; 35:679-689. [DOI: 10.1007/s10585-018-9924-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Accepted: 07/19/2018] [Indexed: 01/08/2023]
|
36
|
Abstract
This overview article for the Comprehensive Physiology collection is focused on detailing platelets, how platelets respond to various stimuli, how platelets interact with their external biochemical environment, and the role of platelets in physiological and pathological processes. Specifically, we will discuss the four major functions of platelets: activation, adhesion, aggregation, and inflammation. We will extend this discussion to include various mechanisms that can induce these functional changes and a discussion of some of the salient receptors that are responsible for platelets interacting with their external environment. We will finish with a discussion of how platelets interact with their vascular environment, with a special focus on interactions with the extracellular matrix and endothelial cells, and finally how platelets can aid and possibly initiate the progression of various vascular diseases. Throughout this overview, we will highlight both the historical investigations into the role of platelets in health and disease as well as some of the more current work. Overall, the authors aim for the readers to gain an appreciation for the complexity of platelet functions and the multifaceted role of platelets in the vascular system. © 2017 American Physiological Society. Compr Physiol 8:1117-1156, 2018.
Collapse
Affiliation(s)
- David A Rubenstein
- Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, USA
| | - Wei Yin
- Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, USA
| |
Collapse
|
37
|
Lescano CH, Freitas de Lima F, Mendes-Silvério CB, Justo AFO, da Silva Baldivia D, Vieira CP, Sanjinez-Argandoña EJ, Cardoso CAL, Mónica FZ, Pires de Oliveira I. Effect of Polyphenols From Campomanesia adamantium on Platelet Aggregation and Inhibition of Cyclooxygenases: Molecular Docking and in Vitro Analysis. Front Pharmacol 2018; 9:617. [PMID: 29946259 PMCID: PMC6005896 DOI: 10.3389/fphar.2018.00617] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2018] [Accepted: 05/23/2018] [Indexed: 12/19/2022] Open
Abstract
Campomanesia adamantium is a medicinal plant of the Brazilian Cerrado. Different parts of its fruits are used in popular medicine to treat gastrointestinal disorders, rheumatism, urinary tract infections and inflammations. Despite its widespread use by the local population, the mechanisms involving platelet aggregation and the inhibition of cyclooxygenase by C. adamantium are unknown. This study evaluated the chemical composition, antioxidant activities and potential benefits of the C. adamantium peel extract (CAPE) and its components in the platelet aggregation induced by arachidonic acid in platelet-rich plasma. Aspects of the pharmacological mechanism were investigated as follows: platelet viability, calcium mobilization, levels of the cyclic nucleotides cAMP and cGMP, thromboxane B2 levels, and the inhibitory effects on COX-1 and COX-2 were studied in vitro and using molecular docking in the catalytic domain of these proteins. The major CAPE constituents standing out from the chemical analysis are the flavonoids, namely those of the flavones and chalcones class. The results showed that CAPE, quercetin and myricetin significantly decreased arachidonic acid-induced platelet aggregation; the assays showed that CAPE and quercetin decreased the mobilization of calcium and thromboxane B2 levels in platelets and increased cAMP and cGMP levels. Moreover, CAPE inhibited the activity of COX-1 and COX-2, highlighting that quercetin could potentially prevent the access of arachidonic acid more to the catalytic site of COX-1 than COX-2. These results highlight CAPE’s potential as a promising therapeutic candidate for the prevention and treatment of diseases associated with platelet aggregation.
Collapse
Affiliation(s)
| | | | | | - Alberto F O Justo
- Department of Pharmacology, University of Campinas, Campinas, Brazil
| | - Débora da Silva Baldivia
- Faculty of Biological and Environmental Sciences, Federal University of Grande Dourados, Dourados, Brazil
| | | | | | - Claudia A L Cardoso
- Center for Natural Resource Studies, University of Mato Grosso do Sul, Dourados, Brazil
| | - Fabíola Z Mónica
- Department of Pharmacology, University of Campinas, Campinas, Brazil
| | - Ivan Pires de Oliveira
- Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| |
Collapse
|
38
|
Kanikarla-Marie P, Lam M, Sorokin AV, Overman MJ, Kopetz S, Menter DG. Platelet Metabolism and Other Targeted Drugs; Potential Impact on Immunotherapy. Front Oncol 2018; 8:107. [PMID: 29732316 PMCID: PMC5919962 DOI: 10.3389/fonc.2018.00107] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2018] [Accepted: 03/27/2018] [Indexed: 12/13/2022] Open
Abstract
The role of platelets in cancer progression has been well recognized in the field of cancer biology. Emerging studies are elaborating further the additional roles and added extent that platelets play in promoting tumorigenesis. Platelets release factors that support tumor growth and also form heterotypic aggregates with tumor cells, which can provide an immune-evasive advantage. Their most critical role may be the inhibition of immune cell function that can negatively impact the body’s ability in preventing tumor establishment and growth. This review summarizes the importance of platelets in tumor progression, therapeutic response, survival, and finally the notion of immunotherapy modulation being likely to benefit from the inclusion of platelet inhibitors.
Collapse
Affiliation(s)
- Preeti Kanikarla-Marie
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Michael Lam
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Alexey V Sorokin
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Michael J Overman
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Scott Kopetz
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - David G Menter
- Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| |
Collapse
|
39
|
Xue L, Xie L, Song X, Song X. Identification of potential tumor-educated platelets RNA biomarkers in non-small-cell lung cancer by integrated bioinformatical analysis. J Clin Lab Anal 2018; 32:e22450. [PMID: 29665143 DOI: 10.1002/jcla.22450] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Accepted: 03/14/2018] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Platelets have emerged as key players in tumorigenesis and tumor progression. Tumor-educated platelet (TEP) RNA profile has the potential to diagnose non-small-cell lung cancer (NSCLC). The objective of this study was to identify potential TEP RNA biomarkers for the diagnosis of NSCLC and to explore the mechanisms in alternations of TEP RNA profile. METHODS The RNA-seq datasets GSE68086 and GSE89843 were downloaded from Gene Expression Omnibus DataSets (GEO DataSets). Then, the functional enrichment of the differentially expressed mRNAs was analyzed by the Database for Annotation Visualization and Integrated Discovery (DAVID). The miRNAs which regulated the differential mRNAs and the target mRNAs of miRNAs were identified by miRanda and miRDB. Then, the miRNA-mRNA regulatory network was visualized via Cytoscape software. RESULTS Twenty consistently altered mRNAs (2 up-regulated and 18 down-regulated) were identified from the two GSE datasets, and they were significantly enriched in several biological processes, including transport and establishment of localization. Twenty identical miRNAs were found between exosomal miRNA-seq dataset and 229 miRNAs that regulated 20 consistently differential mRNAs in platelets. We also analyzed 13 spliceosomal mRNAs and their miRNA predictions; there were 27 common miRNAs between 206 differential exosomal miRNAs and 338 miRNAs that regulated 13 distinct spliceosomal mRNAs. CONCLUSION This study identified 20 potential TEP RNA biomarkers in NSCLC for diagnosis by integrated bioinformatical analysis, and alternations in TEP RNA profile may be related to the post-transcriptional regulation and the splicing metabolisms of spliceosome.
Collapse
Affiliation(s)
- Linlin Xue
- School of Medicine and Life Sciences, Shandong Academy of Medical Sciences, University of Jinan, Jinan, Shandong, China.,Department of Clinical Laboratory, Shandong Academy of Medical Sciences, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Li Xie
- Department of Clinical Laboratory, Shandong Academy of Medical Sciences, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, China.,Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Academy of Medical Sciences, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Xingguo Song
- Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Academy of Medical Sciences, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Xianrang Song
- Department of Clinical Laboratory, Shandong Academy of Medical Sciences, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, China.,Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Academy of Medical Sciences, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, China
| |
Collapse
|
40
|
Smeda M, Kieronska A, Proniewski B, Jasztal A, Selmi A, Wandzel K, Zakrzewska A, Wojcik T, Przyborowski K, Derszniak K, Stojak M, Kaczor D, Buczek E, Watala C, Wietrzyk J, Chlopicki S. Dual antiplatelet therapy with clopidogrel and aspirin increases mortality in 4T1 metastatic breast cancer-bearing mice by inducing vascular mimicry in primary tumour. Oncotarget 2018; 9:17810-17824. [PMID: 29707148 PMCID: PMC5915156 DOI: 10.18632/oncotarget.24891] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Accepted: 02/25/2018] [Indexed: 12/21/2022] Open
Abstract
Platelet inhibition has been considered an effective strategy for combating cancer metastasis and compromising disease malignancy although recent clinical data provided evidence that long-term platelet inhibition might increase incidence of cancer deaths in initially cancer-free patients. In the present study we demonstrated that dual anti-platelet therapy based on aspirin and clopidogrel (ASA+Cl), a routine regiment in cardiovascular patients, when given to cancer-bearing mice injected orthotopically with 4T1 breast cancer cells, promoted progression of the disease and reduced mice survival in association with induction of vascular mimicry (VM) in primary tumour. In contrast, treatment with ASA+Cl or platelet depletion did reduce pulmonary metastasis in mice, if 4T1 cells were injected intravenously. In conclusion, distinct platelet-dependent mechanisms inhibited by ASA+Cl treatment promoted cancer malignancy and VM in the presence of primary tumour and afforded protection against pulmonary metastasis in the absence of primary tumour. In view of our data, long-term inhibition of platelet function by dual anti-platelet therapy (ASA+Cl) might pose a hazard when applied to a patient with undiagnosed and untreated malignant cancer prone to undergo VM.
Collapse
Affiliation(s)
- Marta Smeda
- Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Bobrzynskiego 14, Krakow 30-348, Poland
| | - Anna Kieronska
- Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Bobrzynskiego 14, Krakow 30-348, Poland
| | - Bartosz Proniewski
- Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Bobrzynskiego 14, Krakow 30-348, Poland
| | - Agnieszka Jasztal
- Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Bobrzynskiego 14, Krakow 30-348, Poland
| | - Anna Selmi
- Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Bobrzynskiego 14, Krakow 30-348, Poland
| | - Krystyna Wandzel
- Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Bobrzynskiego 14, Krakow 30-348, Poland
| | - Agnieszka Zakrzewska
- Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Bobrzynskiego 14, Krakow 30-348, Poland
| | - Tomasz Wojcik
- Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Bobrzynskiego 14, Krakow 30-348, Poland
| | - Kamil Przyborowski
- Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Bobrzynskiego 14, Krakow 30-348, Poland
| | - Katarzyna Derszniak
- Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Bobrzynskiego 14, Krakow 30-348, Poland
| | - Marta Stojak
- Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Bobrzynskiego 14, Krakow 30-348, Poland
| | - Dawid Kaczor
- Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Bobrzynskiego 14, Krakow 30-348, Poland
| | - Elzbieta Buczek
- Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Bobrzynskiego 14, Krakow 30-348, Poland
| | - Cezary Watala
- Department of Haemostasis and Haemostatic Disorders, Medical University of Lodz, Kosciuszki 4, Lodz 90-419, Poland
| | - Joanna Wietrzyk
- Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Department of Experimental Oncology, Rudolfa Weigla 4, Wroclaw 53-114, Poland
| | - Stefan Chlopicki
- Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Bobrzynskiego 14, Krakow 30-348, Poland
- Chair of Pharmacology, Jagiellonian University, Medical College, Grzegorzecka 16, Krakow 31-531, Poland
| |
Collapse
|
41
|
Servais L, Wéra O, Dibato Epoh J, Delierneux C, Bouznad N, Rahmouni S, Mazzucchelli G, Baiwir D, Delvenne P, Lancellotti P, Oury C. Platelets contribute to the initiation of colitis-associated cancer by promoting immunosuppression. J Thromb Haemost 2018; 16:762-777. [PMID: 29369476 DOI: 10.1111/jth.13959] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2017] [Indexed: 02/06/2023]
Abstract
Essentials Inflammation plays a key role in the development of colorectal cancer. Understanding mechanisms of cancer initiation might reveal new anticancer preventive strategy. Hyperactive platelets promote tumor formation by fostering immune evasion of cancer. Platelet inhibition by clopidogrel prevents carcinogenesis by restoring antitumor immunity. SUMMARY Background Clinical and experimental evidence support a role for inflammation in the development of colorectal cancer, although the mechanisms are not fully understood. Beyond thrombosis and hemostasis, platelets are key actors in inflammation; they have also been shown to be involved in cancer. However, whether platelets participate in the link between inflammation and cancer is unknown. Objective To investigate the contribution of platelets and platelet-derived proteins to inflammation-elicited colorectal tumor development. Methods We used a clinically relevant mouse model of colitis-associated cancer. Platelet secretion and platelet reactivity to thrombin were assessed at each stage of carcinogenesis. We conducted an unbiased proteomic analysis of releasates of platelets isolated at the pretumoral stage to identify soluble factors that might act on tumor development. Plasma levels of the identified proteins were measured during the course of carcinogenesis. We then treated the mice with clopidogrel to efficiently inhibit platelet release reaction. Results At the pretumoral stage, hyperactive platelets constituted a major source of circulating protumoral serum amyloid A (SAA) proteins. Clopidogrel prevented the early elevation of the plasma SAA protein level, decreased colitis severity, and delayed the formation of dysplastic lesions and adenocarcinoma. Platelet inhibition hindered the expansion and function of immunosuppressive myeloid cells, as well as their infiltration into tumors, but increased the number of tissue CD8+ T cells. Platelets and releasates of platelets from mice with cancer were both able to polarize myeloid cells towards an immunosuppressive phenotype. Conclusions Thus, platelets promote the initiation of colitis-associated cancer by enhancing myeloid cell-dependent immunosuppression. Antiplatelet agents may help to prevent inflammation-elicited carcinogenesis by restoring antitumor immunity.
Collapse
Affiliation(s)
- L Servais
- Laboratory of Thrombosis and Hemostasis and Valvular Heart Disease, GIGA-Cardiovascular Sciences, Department of Cardiology, University of Liège, CHU Sart-Tilman, Liège, Belgium
| | - O Wéra
- Laboratory of Thrombosis and Hemostasis and Valvular Heart Disease, GIGA-Cardiovascular Sciences, Department of Cardiology, University of Liège, CHU Sart-Tilman, Liège, Belgium
| | - J Dibato Epoh
- Laboratory of Thrombosis and Hemostasis and Valvular Heart Disease, GIGA-Cardiovascular Sciences, Department of Cardiology, University of Liège, CHU Sart-Tilman, Liège, Belgium
| | - C Delierneux
- Laboratory of Thrombosis and Hemostasis and Valvular Heart Disease, GIGA-Cardiovascular Sciences, Department of Cardiology, University of Liège, CHU Sart-Tilman, Liège, Belgium
| | - N Bouznad
- Laboratory of Thrombosis and Hemostasis and Valvular Heart Disease, GIGA-Cardiovascular Sciences, Department of Cardiology, University of Liège, CHU Sart-Tilman, Liège, Belgium
| | - S Rahmouni
- Immunology and Infectious Diseases Unit, GIGA-R, University of Liège, Liège, Belgium
| | - G Mazzucchelli
- Laboratory of Mass Spectrometry, Chemistry Department, GIGA-R, CART, University of Liège, Liège, Belgium
| | - D Baiwir
- Laboratory of Mass Spectrometry, Chemistry Department, GIGA-R, CART, University of Liège, Liège, Belgium
| | - P Delvenne
- Department of Pathology, Laboratory of Experimental Pathology, University of Liège, Liège, Belgium
| | - P Lancellotti
- Laboratory of Thrombosis and Hemostasis and Valvular Heart Disease, GIGA-Cardiovascular Sciences, Department of Cardiology, University of Liège, CHU Sart-Tilman, Liège, Belgium
- Gruppo Villa Maria Care and Reseach, Anthea Hospital, Bari, Italy
| | - C Oury
- Laboratory of Thrombosis and Hemostasis and Valvular Heart Disease, GIGA-Cardiovascular Sciences, Department of Cardiology, University of Liège, CHU Sart-Tilman, Liège, Belgium
| |
Collapse
|
42
|
Qi Y, Zhang Y, Fu X, Wang A, Yang Y, Shang Y, Gao Q. Platelet-to-lymphocyte ratio in peripheral blood: A novel independent prognostic factor in patients with melanoma. Int Immunopharmacol 2018; 56:143-147. [DOI: 10.1016/j.intimp.2018.01.019] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2017] [Revised: 12/25/2017] [Accepted: 01/16/2018] [Indexed: 12/26/2022]
|
43
|
Metelli A, Salem M, Wallace CH, Wu BX, Li A, Li X, Li Z. Immunoregulatory functions and the therapeutic implications of GARP-TGF-β in inflammation and cancer. J Hematol Oncol 2018; 11:24. [PMID: 29458436 PMCID: PMC5819195 DOI: 10.1186/s13045-018-0570-z] [Citation(s) in RCA: 75] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Accepted: 02/06/2018] [Indexed: 12/12/2022] Open
Abstract
GARP (glycoprotein-A repetitions predominant) is a type I transmembrane cell surface docking receptor for latent transforming growth factor-β (TGF-β) that is abundantly expressed on regulatory T lymphocytes and platelets. GARP regulates the availability of membrane-bound latent TGF-β and modulates its activation. For this reason, GARP expression on immune and non-immune cells is involved in maintaining peripheral tolerance. It plays an important role in preventing inflammatory diseases such as allergy and graft versus host disease (GvHD). GARP is also frequently hijacked by cancer cells to promote oncogenesis. This review summarizes the most important features of GARP biology described to date including gene regulation, protein expression and mechanism in activating latent TGF-β, and the function of GARP in regulatory T cell biology and peripheral tolerance, as well as GARP’s increasingly recognized roles in platelet-mediated cancer immune evasion. The promise for GARP-targeted strategy as a novel immunotherapy of cancer is also highlighted.
Collapse
Affiliation(s)
- Alessandra Metelli
- Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Mohammad Salem
- Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Caroline H Wallace
- Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Bill X Wu
- Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Anqi Li
- Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Xue Li
- Children's Hospital Boston, Harvard Medical School, Boston, MA, 02115, USA
| | - Zihai Li
- Department of Microbiology and Immunology, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, 29425, USA. .,The First Affiliated Hospital, Zhengzhou University School of Medicine, Zhengzhou, 450052, China.
| |
Collapse
|
44
|
Yang J, Xu H, Guo X, Zhang J, Ye X, Yang Y, Ma X. Pretreatment Inflammatory Indexes as Prognostic Predictors for Survival in Colorectal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy. Sci Rep 2018; 8:3044. [PMID: 29445100 PMCID: PMC5813153 DOI: 10.1038/s41598-018-21093-7] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Accepted: 01/30/2018] [Indexed: 02/05/2023] Open
Abstract
This study was to evaluate the prognostic value of pretreatment inflammatory indexes including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) in colorectal cancer (CRC) patients receiving neoadjuvant chemoradiotherapy (CRT). We enrolled 98 eligible CRC patients and divided them into high or low NLR, PLR, LMR, and SII groups according to their median index value, respectively. Univariate and multivariate analysis were performed to identify the potential predictors of progression-free survival (PFS) and overall survival (OS). In the univariate analysis, ECOG performance status, distant metastasis, NLR, PLR, LMR, and SII were found to be significantly associated with PFS and OS. In the multivariate analysis, ECOG performance status, distant metastasis, and NLR were identified to be independent predictors of PFS (HR 2.487, p = 0.012; HR 2.422, p = 0.042; HR 2.243, p = 0.034, respectively), and OS (HR 2.237, p = 0.018; HR 2.757, p = 0.020; HR 2.336, p = 0.017, respectively). The results of our study revealed that ECOG performance status, distant metastasis and NLR were independent prognostic factors of PFS and OS in CRC patients receiving neoadjuvant CRT.
Collapse
Affiliation(s)
- Jing Yang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Hui Xu
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, 610041, PR China
| | - Xinli Guo
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Jing Zhang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Xiaoyang Ye
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Yanping Yang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Xuelei Ma
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
| |
Collapse
|
45
|
Li W, Tao L, Lu M, Xiu D. Prognostic role of platelet to lymphocyte ratio in pancreatic cancers: A meta-analysis including 3028 patients. Medicine (Baltimore) 2018; 97:e9616. [PMID: 29465553 PMCID: PMC5841988 DOI: 10.1097/md.0000000000009616] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Platelet to lymphocyte ratio (PLR) was recently reported being associated with the prognosis of pancreatic cancer (PC), but the prognostic value of PLR in pancreatic cancer remains inconsistent. We conduct a meta-analysis to evaluate the prognostic role of PLR in patients with PC. METHODS PubMed, Embase, Cochrane Library, and Web of Science were systematically searched for eligible studies which investigated the relationship between PLR and clinical outcome of patients with pancreatic cancer. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the prognostic role of PLR in overall survival (OS) and progression-free survival (PFS)/time to progression (TTP). RESULTS A total of 16 studies comprising 3028 patients with PC were enrolled in this meta-analysis. Pooled analysis demonstrated that elevated PLR predicted a poor OS (HR = 1.22, 95% CI: 1.09-1.36, P < .001). Prognostic role of PLR on OS were significant in subgroup of Asians (HR = 1.22, 95% CI: 1.11-1.34, P < .001), patients treated with chemotherapy (HR = 1.18, 95% CI: 1.04-1.35, P = .01) and mixed methods (HR = 1.29, 95% CI: 1.07-1.57, P = .009), American joint committee on cancer (AJCC) stage of III-IV (HR = 1.22, 95% CI: 1.09-1.36, P < .001), pathological subtype of pancreatic adenocarcinoma (HR = 1.21, 95% CI: 1.08-1.36, P = .001), and cut-off value of PLR ≥160 (HR = 1.48, 95% CI: 1.25-1.75, P < .001). CONCLUSIONS An elevated PLR is associated with unfavorable overall survival in patients with pancreatic cancer.
Collapse
|
46
|
Strohkamp S, Gemoll T, Humborg S, Hartwig S, Lehr S, Freitag-Wolf S, Becker S, Franzén B, Pries R, Wollenberg B, Roblick UJ, Bruch HP, Keck T, Auer G, Habermann JK. Protein levels of clusterin and glutathione synthetase in platelets allow for early detection of colorectal cancer. Cell Mol Life Sci 2018; 75:323-334. [PMID: 28849249 PMCID: PMC11105233 DOI: 10.1007/s00018-017-2631-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2017] [Revised: 07/21/2017] [Accepted: 08/21/2017] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) is one of the most frequent malignancies in the Western world. Early tumor detection and intervention are important determinants on CRC patient survival. During early tumor proliferation, dissemination and angiogenesis, platelets store and segregate proteins actively and selectively. Hence, the platelet proteome is a potential source of biomarkers denoting early malignancy. By comparing protein profiles of platelets between healthy volunteers (n = 12) and patients with early- (n = 7) and late-stage (n = 5) CRCs using multiplex fluorescence two-dimensional gel electrophoresis (2D-DIGE), we aimed at identifying differentially regulated proteins within platelets. By inter-group comparisons, 94 differentially expressed protein spots were detected (p < 0.05) between healthy controls and patients with early- and late-stage CRCs and revealed distinct separations between all three groups in principal component analyses. 54 proteins of interest were identified by mass spectrometry and resulted in high-ranked Ingenuity Pathway Analysis networks associated with Cellular function and maintenance, Cellular assembly and organization, Developmental disorder and Organismal injury and abnormalities (p < 0.0001 to p = 0.0495). Target proteins were validated by multiplex fluorescence-based Western blot analyses using an additional, independent cohort of platelet protein samples [healthy controls (n = 15), early-stage CRCs (n = 15), late-stage CRCs (n = 15)]. Two proteins-clusterin and glutathione synthetase (GSH-S)-featured high impact and were subsequently validated in this independent clinical cohort distinguishing healthy controls from patients with early- and late-stage CRCs. Thus, the potential of clusterin and GSH-S as platelet biomarkers for early detection of CRC could improve existing screening modalities in clinical application and should be confirmed in a prospective multicenter trial.
Collapse
Affiliation(s)
- Sarah Strohkamp
- Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany
| | - Timo Gemoll
- Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
| | - Sina Humborg
- Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany
| | - Sonja Hartwig
- Institute of Clinical Biochemistry and Pathobiochemistry, Leibniz Center for Diabetes Research, German Diabetes Center at the Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Stefan Lehr
- Institute of Clinical Biochemistry and Pathobiochemistry, Leibniz Center for Diabetes Research, German Diabetes Center at the Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Sandra Freitag-Wolf
- Institute of Medical Informatics and Statistics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany
| | - Susanne Becker
- Karolinska Biomics Center, Karolinska Institutet, Stockholm, Sweden
| | - Bo Franzén
- Karolinska Biomics Center, Karolinska Institutet, Stockholm, Sweden
| | - Ralph Pries
- Clinic for Otorhinolaryngology, Head and Neck Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Barbara Wollenberg
- Clinic for Otorhinolaryngology, Head and Neck Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Uwe J Roblick
- Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany
| | - Hans-Peter Bruch
- Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany
| | - Tobias Keck
- Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany
| | - Gert Auer
- Karolinska Biomics Center, Karolinska Institutet, Stockholm, Sweden
| | - Jens K Habermann
- Section for Translational Surgical Oncology and Biobanking, Department of Surgery, University of Lübeck and University Medical Center Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Germany.
- Interdisciplinary Center for Biobanking-Lübeck (ICB-L), University of Lübeck, Lübeck, Germany.
| |
Collapse
|
47
|
Yang J, Guo X, Wang M, Ma X, Ye X, Lin P. Pre-treatment inflammatory indexes as predictors of survival and cetuximab efficacy in metastatic colorectal cancer patients with wild-type RAS. Sci Rep 2017; 7:17166. [PMID: 29215037 PMCID: PMC5719445 DOI: 10.1038/s41598-017-17130-6] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2017] [Accepted: 11/22/2017] [Indexed: 02/05/2023] Open
Abstract
This study aims at evaluating the prognostic significance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation indexes (SII) in metastatic colorectal cancer (mCRC) patients treated with cetuximab. Ninety-five patients receiving cetuximab for mCRC were categorized into the high or low NLR, PLR, LMR, and SII groups based on their median index values. Univariate and multivariate survival analysis were performed to identify the indexes’ correlation with progression-free survival (PFS) and overall survival (OS). In the univariate analysis, ECOG performance status, neutrphil counts, lymphocyte counts, monocyte counts, NLR, PLR, and LDH were associated with survival. Multivariate analysis showed that ECOG performance status of 0 (hazard ratio [HR] 3.608, p < 0.001; HR 5.030, p < 0.001, respectively), high absolute neutrophil counts (HR 2.837, p < 0.001; HR 1.922, p = 0.026, respectively), low lymphocyte counts (HR 0.352, p < 0.001; HR 0.440, p = 0.001, respectively), elevated NLR (HR 3.837, p < 0.001; HR 2.467, p = 0.006) were independent predictors of shorter PFS and OS. In conclusion, pre-treatment inflammatory indexes, especially NLR were potential biomarkers to predict the survival of mCRC patients with cetuximab therapy.
Collapse
Affiliation(s)
- Jing Yang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Xinli Guo
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Manni Wang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China
| | - Xuelei Ma
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
| | - Xiaoyang Ye
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, 610041, PR China
| | - Panpan Lin
- West China School of Medicine, West China Hospital, Sichuan University, Chengdu, 610041, PR China
| |
Collapse
|
48
|
Chockley PJ, Keshamouni VG. Immunological Consequences of Epithelial-Mesenchymal Transition in Tumor Progression. THE JOURNAL OF IMMUNOLOGY 2017; 197:691-8. [PMID: 27431984 DOI: 10.4049/jimmunol.1600458] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 03/16/2016] [Accepted: 05/18/2016] [Indexed: 12/26/2022]
Abstract
Microenvironments that tumor cells encounter are different during the stages of cancer progression-primary tumor, metastasis, and at the metastatic site. This suggests potential differences in immune surveillance of primary tumor and metastasis. Epithelial-mesenchymal transition (EMT) is a key reversible process in which cancer cells transition into highly motile and invasive cells for dissemination. Only a tiny proportion successfully metastasize, supporting the notion of metastasis-specific immune surveillance. EMT involves extensive molecular reprogramming of cells conferring many clinically relevant features to cancer cells and affects tumor cell interactions within the tumor microenvironment. We review the impact of tumor immune infiltrates on tumor cell EMT and the consequences of EMT in shaping the immune microenvironment of tumors. The usefulness of EMT as a model to investigate metastasis-specific immune surveillance mechanisms are also explored. Finally, we discuss potential implications of EMT for tumor immunogenicity, as well as current immunotherapies and future strategies.
Collapse
Affiliation(s)
- Peter J Chockley
- Graduate Program in Immunology, University of Michigan Medical Center, Ann Arbor, MI 48109; and
| | - Venkateshwar G Keshamouni
- Graduate Program in Immunology, University of Michigan Medical Center, Ann Arbor, MI 48109; and Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109
| |
Collapse
|
49
|
Sun Z, Ju Y, Han F, Sun X, Wang F. Clinical implications of pretreatment inflammatory biomarkers as independent prognostic indicators in prostate cancer. J Clin Lab Anal 2017; 32. [PMID: 28605139 DOI: 10.1002/jcla.22277] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2017] [Accepted: 05/16/2017] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVES Research on the relationship between inflammatory biomarkers and malignant tumors has become a hotspot. Many studies have demonstrated that neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and red blood cell distribution width (RDW) could act as independent prognostic indicators for several solid tumors. This study aimed to evaluate the clinical implications of pretreatment inflammatory biomarkers, including NLR, PLR, and RDW as independent prognostic indicators in prostate cancer (PCa). METHODS A total of 226 PCa patients who were diagnosed at our institution from 2011 to 2016 were analyzed retrospectively. We compared the clinicopathological features, survival curves, and prognosis of the PCa patients between the high and low groups according to the cutoffs of NLR, PLR, and RDW. RESULTS The pretreatment NLR, PLR, and RDW values were significantly higher in the patients with PCa than those in the controls (P<.05). Increased NLR and PLR values were significantly associated with high risk of progression, including higher Gleason scores, cell proliferation antigen 67 (Ki-67) indexes, and prostate-specific antigen (PSA) levels (P<.05), whereas an elevated RDW was only associated with an older age. An increased NLR was correlated with both overall survival (OS) (P=.025) and disease-free survival (DFS) (P=.017). In addition, a higher PLR only showed a significantly worse DFS (P=.040). Pretreatment NLR was an independent prognostic indicator of DFS. CONCLUSIONS The pretreatment NLR and PLR might be beneficial to predict the progression and prognosis of PCa. Furthermore, NLR was more effective than PLR acting as an independent prognostic indicator for PCa.
Collapse
Affiliation(s)
- Zhaohui Sun
- Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, China
| | - Ying Ju
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Fuyan Han
- Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China
| | - Xiya Sun
- School of Basic Medical Sciences of Lanzhou University, Lanzhou, Gansu, China
| | - Fang Wang
- Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong, China
| |
Collapse
|
50
|
Reflections on multiple strategies to reduce transfusion in cancer patients: A joint narrative. Transfus Apher Sci 2017; 56:322-329. [DOI: 10.1016/j.transci.2017.05.018] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
|