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Novoa Díaz MB, Gentili C, Martín MJ, Carriere P. Prognosis in stage II colon cancer: Expanding the horizons of risk factors. World J Gastrointest Oncol 2025; 17:100552. [PMID: 39958547 PMCID: PMC11756003 DOI: 10.4251/wjgo.v17.i2.100552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 10/31/2024] [Accepted: 11/20/2024] [Indexed: 01/18/2025] Open
Abstract
In the following editorial, we discuss the article by Wu et al. In this contribution, we critically review the authors' perspective and analyze the relevance of the results obtained in the original article of clinical research by Liu et al. We consider that additional factors associated with colon cancer progression have recently been described in extensive clinical research, and should be included in this analysis to achieve a more accurate prognosis. These factors include inflammation, gut microbiota composition, immune status and nutritional balance, as they influence the post-surgical survival profile of patients with stage II colorectal cancer. We also address the clinical implementation and limitations of these analyses. Evaluation of the patient´s entire context is essential for selection of the most appropriate therapy.
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Affiliation(s)
- María Belén Novoa Díaz
- Department of Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS)-INBIOSUR (CONICET-UNS), Bahía Blanca 8000, Buenos Aires, Argentina
| | - Claudia Gentili
- Department of Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS)-INBIOSUR (CONICET-UNS), Bahía Blanca 8000, Buenos Aires, Argentina
| | - María Julia Martín
- Department of Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS)-INIBIBB (CONICET-UNS), Bahía Blanca 8000, Buenos Aires, Argentina
| | - Pedro Carriere
- Department of Biología, Bioquímica y Farmacia, Universidad Nacional del Sur (UNS)-INBIOSUR (CONICET-UNS), Bahía Blanca 8000, Buenos Aires, Argentina
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Dang Q, Zuo L, Hu X, Zhou Z, Chen S, Liu S, Ba Y, Zuo A, Xu H, Weng S, Zhang Y, Luo P, Cheng Q, Liu Z, Han X. Molecular subtypes of colorectal cancer in the era of precision oncotherapy: Current inspirations and future challenges. Cancer Med 2024; 13:e70041. [PMID: 39054866 PMCID: PMC11272957 DOI: 10.1002/cam4.70041] [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: 03/29/2024] [Revised: 07/07/2024] [Accepted: 07/12/2024] [Indexed: 07/27/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is among the most hackneyed malignancies. Even patients with identical clinical symptoms and the same TNM stage still exhibit radically different clinical outcomes after receiving equivalent treatment regimens, indicating extensive heterogeneity of CRC. Myriad molecular subtypes of CRC have been exploited for decades, including the most compelling consensus molecular subtype (CMS) classification that has been broadly applied for patient stratification and biomarker-drug combination formulation. Encountering barriers to clinical translation, however, CMS classification fails to fully reflect inter- or intra-tumor heterogeneity of CRC. As a consequence, addressing heterogeneity and precisely managing CRC patients with unique characteristics remain arduous tasks for clinicians. REVIEW In this review, we systematically summarize molecular subtypes of CRC and further elaborate on their clinical applications, limitations, and future orientations. CONCLUSION In recent years, exploration of subtypes through cell lines, animal models, patient-derived xenografts (PDXs), organoids, and clinical trials contributes to refining biological insights and unraveling subtype-specific therapies in CRC. Therapeutic interventions including nanotechnology, clustered regulatory interspaced short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9), gut microbiome, and liquid biopsy are powerful tools with the possibility to shift the immunologic landscape and outlook for CRC precise medicine.
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Affiliation(s)
- Qin Dang
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
- Department of Colorectal SurgeryThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Lulu Zuo
- Center for Reproductive MedicineThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Xinru Hu
- Department of Cardiology, West China HospitalSichuan UniversityChengduSichuanChina
| | - Zhaokai Zhou
- Department of UrologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Shuang Chen
- Center for Reproductive MedicineThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Shutong Liu
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Yuhao Ba
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Anning Zuo
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Hui Xu
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Siyuan Weng
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Yuyuan Zhang
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Peng Luo
- Department of Oncology, Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdongChina
| | - Quan Cheng
- Department of Neurosurgery, Xiangya HospitalCentral South UniversityChangshaHunanChina
| | - Zaoqu Liu
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
- Interventional Treatment and Clinical Research Center of Henan ProvinceZhengzhouHenanChina
- Interventional Institute of Zhengzhou UniversityZhengzhouHenanChina
- Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Xinwei Han
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
- Interventional Treatment and Clinical Research Center of Henan ProvinceZhengzhouHenanChina
- Interventional Institute of Zhengzhou UniversityZhengzhouHenanChina
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Sgarzi M, Mazzeschi M, Santi S, Montacci E, Panciera T, Ferlizza E, Girone C, Morselli A, Gelfo V, Kuhre RS, Cavallo C, Valente S, Pasquinelli G, Győrffy B, D'Uva G, Romaniello D, Lauriola M. Aberrant MET activation impairs perinuclear actin cap organization with YAP1 cytosolic relocation. Commun Biol 2023; 6:1044. [PMID: 37838732 PMCID: PMC10576810 DOI: 10.1038/s42003-023-05411-y] [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: 12/17/2022] [Accepted: 10/03/2023] [Indexed: 10/16/2023] Open
Abstract
Little is known about the signaling network responsible for the organization of the perinuclear actin cap, a recently identified structure holding unique roles in the regulation of nuclear shape and cell directionality. In cancer cells expressing a constitutively active MET, we show a rearrangement of the actin cap filaments, which crash into perinuclear patches associated with spherical nuclei, meandering cell motility and inactivation of the mechano-transducer YAP1. MET ablation is sufficient to reactivate YAP1 and restore the cap, leading to enhanced directionality and flattened nuclei. Consistently, the introduction of a hyperactive MET in normal epithelial cells, enhances nuclear height and alters the cap organization, as also confirmed by TEM analysis. Finally, the constitutively active YAP1 mutant YAP5SA is able to overcome the effects of oncogenic MET. Overall, our work describes a signaling axis empowering MET-mediated YAP1 dampening and actin cap misalignment, with implications for nuclear shape and cell motility.
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Affiliation(s)
- Michela Sgarzi
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | | | - Spartaco Santi
- Institute of Molecular Genetics, National Research Council of Italy, Bologna, Italy
- IRCCS-Institute Orthopaedic Rizzoli, Bologna, Italy
| | - Elisa Montacci
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Tito Panciera
- Department of Molecular Medicine, University of Padua, Padua, Italy
| | - Enea Ferlizza
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Cinzia Girone
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Alessandra Morselli
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Valerio Gelfo
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Rikke Sofie Kuhre
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Carola Cavallo
- Laboratory of Preclinical Studies for Regenerative Medicine of the Musculoskeletal System (RAMSES), (IRCCS) Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Sabrina Valente
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Gianandrea Pasquinelli
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Balazs Győrffy
- Semmelweis University Dept. of Bioinformatics and 2nd Dept. Of Pediatrics, Budapest, Hungary
- TTK Cancer Biomarker Research Group, Institute of Enzymology, Budapest, Hungary
| | - Gabriele D'Uva
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy
| | - Donatella Romaniello
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
| | - Mattia Lauriola
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy.
- Centre for Applied Biomedical Research (CRBA), Bologna University Hospital Authority St. Orsola -Malpighi Polyclinic, Bologna, Italy.
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Dobbs Spendlove M, M. Gibson T, McCain S, Stone BC, Gill T, Pickett BE. Pathway2Targets: an open-source pathway-based approach to repurpose therapeutic drugs and prioritize human targets. PeerJ 2023; 11:e16088. [PMID: 37790614 PMCID: PMC10544355 DOI: 10.7717/peerj.16088] [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: 03/28/2023] [Accepted: 08/22/2023] [Indexed: 10/05/2023] Open
Abstract
Background Recent efforts to repurpose existing drugs to different indications have been accompanied by a number of computational methods, which incorporate protein-protein interaction networks and signaling pathways, to aid with prioritizing existing targets and/or drugs. However, many of these existing methods are focused on integrating additional data that are only available for a small subset of diseases or conditions. Methods We have designed and implemented a new R-based open-source target prioritization and repurposing method that integrates both canonical intracellular signaling information from five public pathway databases and target information from public sources including OpenTargets.org. The Pathway2Targets algorithm takes a list of significant pathways as input, then retrieves and integrates public data for all targets within those pathways for a given condition. It also incorporates a weighting scheme that is customizable by the user to support a variety of use cases including target prioritization, drug repurposing, and identifying novel targets that are biologically relevant for a different indication. Results As a proof of concept, we applied this algorithm to a public colorectal cancer RNA-sequencing dataset with 144 case and control samples. Our analysis identified 430 targets and ~700 unique drugs based on differential gene expression and signaling pathway enrichment. We found that our highest-ranked predicted targets were significantly enriched in targets with FDA-approved therapeutics for colorectal cancer (p-value < 0.025) that included EGFR, VEGFA, and PTGS2. Interestingly, there was no statistically significant enrichment of targets for other cancers in this same list suggesting high specificity of the results. We also adjusted the weighting scheme to prioritize more novel targets for CRC. This second analysis revealed epidermal growth factor receptor (EGFR), phosphoinositide-3-kinase (PI3K), and two mitogen-activated protein kinases (MAPK14 and MAPK3). These observations suggest that our open-source method with a customizable weighting scheme can accurately prioritize targets that are specific and relevant to the disease or condition of interest, as well as targets that are at earlier stages of development. We anticipate that this method will complement other approaches to repurpose drugs for a variety of indications, which can contribute to the improvement of the quality of life and overall health of such patients.
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Affiliation(s)
- Mauri Dobbs Spendlove
- Microbiology and Molecular Biology, Brigham Young University, Provo, UT, United States of America
| | - Trenton M. Gibson
- Microbiology and Molecular Biology, Brigham Young University, Provo, UT, United States of America
| | - Shaney McCain
- Microbiology and Molecular Biology, Brigham Young University, Provo, UT, United States of America
| | - Benjamin C. Stone
- Microbiology and Molecular Biology, Brigham Young University, Provo, UT, United States of America
| | | | - Brett E. Pickett
- Microbiology and Molecular Biology, Brigham Young University, Provo, UT, United States of America
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Shi ZY, Zhang SX, Li CH, Fan D, Xue Y, Cheng ZH, Wu LX, Lu KY, Wu ZF, Li XF, Liu HY, Li SJ. Differential distribution and prognostic value of CD4+ T cell subsets before and after radioactive iodine therapy in differentiated thyroid cancer with varied curative outcomes. Front Immunol 2022; 13:966550. [PMID: 36091039 PMCID: PMC9459039 DOI: 10.3389/fimmu.2022.966550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 08/11/2022] [Indexed: 12/24/2022] Open
Abstract
Differentiated thyroid cancer is the most frequently diagnosed endocrine tumor. While differentiated thyroid cancers often respond to initial treatment, little is known about the differences in circulating immune cells amongst patients who respond differently. A prospective study of 39 patients with differentiated thyroid cancer was conducted. Serum thyroglobulin levels and thyroid and immunological functions were tested before and after radioactive iodine treatment (RAIT). Efficacy assessments were performed 6 to 12 months after radioactive iodine treatment. Most patients showed an excellent response to radioactive iodine treatment. Before radioactive iodine treatment, the excellent response group had considerably fewer circulating CD4+ T cell subsets than the non-excellent response group. Both the excellent response and non-excellent response groups had considerably lower circulating CD4+ T lymphocyte subsets 30 days after radioactive iodine treatment, but those of the excellent response group were still lower than those of the non-excellent response group. All circulating CD4+ T cell subsets in the excellent response group rose by varying degrees by the 90th day, but only Treg cell amounts increased in the non-excellent response group. Interestingly, in the non-excellent response group, we noticed a steady drop in Th1 cells. However, the bulk of circulating CD4+ T cell subsets between the two groups did not differ appreciably by the 90th day. Finally, we discovered that CD4+ T cell subsets had strong predictive potential, and we thus developed high-predictive-performance models that deliver more dependable prognostic information. In conclusion, in individuals with differentiated thyroid cancer, there is great variation in circulating immune cells, resulting in distinct treatment outcomes. Low absolute CD4+ T cell counts is linked to improved clinical outcomes as well as stronger adaptive and resilience capacities.
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Affiliation(s)
- Zhi-Yong Shi
- Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
- Collaborative Innovation Center for Molecular Imaging of Precision Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Sheng-Xiao Zhang
- Department of Rheumatology, Second Hospital of Shanxi Medical University, Taiyuan, China
- Key laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China
| | - Cai-Hong Li
- Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
- Collaborative Innovation Center for Molecular Imaging of Precision Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Di Fan
- Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
- Collaborative Innovation Center for Molecular Imaging of Precision Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Yan Xue
- Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
- Collaborative Innovation Center for Molecular Imaging of Precision Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Zhe-Hao Cheng
- Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
- Collaborative Innovation Center for Molecular Imaging of Precision Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Li-Xiang Wu
- Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
- Collaborative Innovation Center for Molecular Imaging of Precision Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Ke-Yi Lu
- Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
- Collaborative Innovation Center for Molecular Imaging of Precision Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Zhi-Fang Wu
- Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
- Collaborative Innovation Center for Molecular Imaging of Precision Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Xiao-Feng Li
- Department of Rheumatology, Second Hospital of Shanxi Medical University, Taiyuan, China
| | - Hai-Yan Liu
- Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
- Collaborative Innovation Center for Molecular Imaging of Precision Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
- *Correspondence: Hai-Yan Liu, ; Si-Jin Li,
| | - Si-Jin Li
- Department of Nuclear Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
- Collaborative Innovation Center for Molecular Imaging of Precision Medicine, First Hospital of Shanxi Medical University, Taiyuan, China
- Department of Rheumatology, Second Hospital of Shanxi Medical University, Taiyuan, China
- *Correspondence: Hai-Yan Liu, ; Si-Jin Li,
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