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de Paula Filho MFF, Lopes Chrisóstomo LL, Cansanção IF. HPV16 Genomes: In Silico Analysis of E6 and E7 Oncoproteins in 20 South American Variants. Curr Genomics 2024; 25:316-321. [PMID: 39156730 PMCID: PMC11327806 DOI: 10.2174/0113892029293113240427065916] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 03/19/2024] [Accepted: 03/31/2024] [Indexed: 08/20/2024] Open
Abstract
Background Human papillomavirus (HPV) is the main risk factor for the development of squamous cell cervical cancer, and E6 oncoprotein and E7 oncoprotein are important components of the viral genome and its oncogenic potential. It is known that different viral variants of HPV16 have different pathology and impact on the development of neoplasia, although few studies have been performed on South American variants. Objective Therefore, the present study aimed to analyze in silico the genomic diversity of HPV16 in 20 complete genome variants of South America in the National Center for Biotechnology Information (NCBI) database. Methods We performed a descriptive study to characterize the polymorphic regions of the E6 and E7 genes in HPV16 variants, using software for genomic data and single nucleotide polymorphism (SNP) analysis and others for phylogenetic analysis. Results The variants analyzed included six SNPs linked to cancer (A131G, G145T, C335T, T350G, C712A, and T732C) and significant variation (798 nucleotide substitutions). Despite this, the variants showed low genetic diversity. Eighteen variants of unclear significance (VUS) were identified, 10 of which were in the coding E6 regions and 8 in the coding E7 regions. The prevalence of lineage D variants is of concern due to their pathology in cervical cancer and requires more research and epidemiological vigilance regarding their prevalence in the population. Conclusion The data obtained in this study may contribute to future research on South American variants of HPV16, their pathogenicity, and the development of treatments.
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Affiliation(s)
| | - Lara Luísa Lopes Chrisóstomo
- Medicine Collegiate, Campus Paulo Afonso, Universidade Federal do Vale do São Francisco (UNIVASF), Paulo Afonso, BA, 48605-780, Brazil
| | - Isaac Farias Cansanção
- Medicine Collegiate, Campus Paulo Afonso, Universidade Federal do Vale do São Francisco (UNIVASF), Paulo Afonso, BA, 48605-780, Brazil
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Maiti A, Okano I, Oshi M, Okano M, Tian W, Kawaguchi T, Katsuta E, Takabe K, Yan L, Patnaik SK, Hait NC. Altered Expression of Secreted Mediator Genes That Mediate Aggressive Breast Cancer Metastasis to Distant Organs. Cancers (Basel) 2021; 13:cancers13112641. [PMID: 34072157 PMCID: PMC8199412 DOI: 10.3390/cancers13112641] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2021] [Revised: 05/11/2021] [Accepted: 05/21/2021] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Heterogeneity is the characteristic of breast tumors, making it difficult to understand the molecular mechanism. Alteration of gene expression in the primary tumor versus the metastatic lesion remains challenging for getting any specific targeted therapy. To better understand how gene expression profile changes during metastasis, we compare the primary tumor and distant metastatic tumor gene expression using primary breast tumors compared with its metastatic variant in animal models. Our RNA sequencing data from cells revealed that parental cell and the metastatic variant cell are different in gene expression while gene signature significantly altered during metastasis to distant organs than primary breast tumors. We found that secreted mediators encoding genes (ANGPTL7, MMP3, LCN2, S100A8, and ESM1) are correlated with poor prognosis in the clinical setting as divulged from METABRIC and TCGA-BRCA cohort data analysis. Abstract Due to the heterogeneous nature of breast cancer, metastasis organotropism has been poorly understood. This study assessed the specific cancer-related gene expression changes occurring with metastatic breast cancer recurrence to distant organs compared with non-metastatic breast cancer. We found that several secreted mediators encoding genes notably, LCN2 and S100A8 overexpressed at the distant metastatic site spine (LCN2, 5-fold; S100A8, 6-fold) and bone (LCN2, 5-fold; S100A8, 3-fold) vs. primary tumors in the syngeneic implantation/tumor-resection metastasis mouse model. In contrast, the ESM-1 encoding gene is overexpressed in the primary tumors and markedly downregulated at distant metastatic sites. Further digging into TCAGA-BRCA, SCAN-B, and METABRIC cohorts data analysis revealed that LCN2, S100A8, and ESM-1 mediators encoding individual gene expression scores were strongly associated with disease-specific survival (DSS) in the METABRIC cohort (hazard ratio (HR) > 1, p < 0.0004). The gene expression scores predicted worse clinically aggressive tumors, such as high Nottingham histological grade and advanced cancer staging. Higher gene expression score of ESM-1 gene was strongly associated with worse overall survival (OS) in the triple-negative breast cancer (TNBC) and hormonal receptor (HR)-positive/HER2-negative subtype in METABRIC cohort, HER2+ subtype in TCGA-BRCA and SCAN-B breast cancer cohorts. Our data suggested that mediators encoding genes with prognostic and predictive values may be clinically useful for breast cancer spine, bone, and lung metastasis, particularly in more aggressive subtypes such as TNBC and HER2+ breast cancer.
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Affiliation(s)
- Aparna Maiti
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (I.O.); (M.O.); (M.O.); (T.K.); (E.K.); (K.T.)
- Department of Molecular & Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
- Correspondence: (A.M.); (N.C.H.); Tel.: +1-(716)-845-3505 (A.M.); +1-(716)-845-8527 (N.C.H.); Fax: +1-(716)-845-1668 (N.C.H.)
| | - Ichiro Okano
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (I.O.); (M.O.); (M.O.); (T.K.); (E.K.); (K.T.)
| | - Masanori Oshi
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (I.O.); (M.O.); (M.O.); (T.K.); (E.K.); (K.T.)
| | - Maiko Okano
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (I.O.); (M.O.); (M.O.); (T.K.); (E.K.); (K.T.)
| | - Wanqing Tian
- Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (W.T.); (L.Y.)
| | - Tsutomu Kawaguchi
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (I.O.); (M.O.); (M.O.); (T.K.); (E.K.); (K.T.)
| | - Eriko Katsuta
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (I.O.); (M.O.); (M.O.); (T.K.); (E.K.); (K.T.)
| | - Kazuaki Takabe
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (I.O.); (M.O.); (M.O.); (T.K.); (E.K.); (K.T.)
| | - Li Yan
- Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (W.T.); (L.Y.)
| | - Santosh K. Patnaik
- Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;
| | - Nitai C. Hait
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (I.O.); (M.O.); (M.O.); (T.K.); (E.K.); (K.T.)
- Department of Molecular & Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
- Correspondence: (A.M.); (N.C.H.); Tel.: +1-(716)-845-3505 (A.M.); +1-(716)-845-8527 (N.C.H.); Fax: +1-(716)-845-1668 (N.C.H.)
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Albertsmeier M, Riedl K, Stephan AJ, Drefs M, Schiergens TS, Engel J, Angele MK, Werner J, Guba M. Improved survival after resection of colorectal liver metastases in patients with unresectable lung metastases. HPB (Oxford) 2020; 22:368-375. [PMID: 31399325 DOI: 10.1016/j.hpb.2019.07.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Revised: 05/19/2019] [Accepted: 07/09/2019] [Indexed: 12/12/2022]
Abstract
BACKGROUND Modern systemic therapies considerably improve tumour control and thus open the possibility of new surgical approaches in metastatic colorectal cancer. In this retrospective clinical cohort with a comparison group, we investigated whether liver resection in a combined liver-lung-metastasised stage is justified if pulmonary disease is not resected. METHODS From 283 patients treated in our institution between 2000 and 2014 for combined colorectal liver- and lung metastases, 35 patients had their pulmonary metastases left in situ while they were eligible for both treatment options: resection versus non-resection of liver metastases. Effectively, 15 of these patients received whereas 20 did not receive a liver resection. In these patients, we compared overall survival and determined risk factors that are associated with poor survival, applying a Cox-Proportional Hazards model. RESULTS Patients whose liver metastases were resected showed significantly longer median survival compared to patients who did not undergo hepatic surgery (median 2.6 vs 1.5 years, P = 0.0182). The Cox-Proportional Hazards model revealed hepatic metastasectomy to be the strongest determinant of patient survival (HR 5.27; CI: (1.89, 14.65)). CONCLUSION Our results suggest that surgical removal of liver metastases may be beneficial in selected patients even if concomitant lung metastases cannot be resected.
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Affiliation(s)
- Markus Albertsmeier
- Department of General, Visceral and Transplantation Surgery, University Hospital of Munich, Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany.
| | - Kathrin Riedl
- Department of General, Visceral and Transplantation Surgery, University Hospital of Munich, Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany
| | - Anna-Janina Stephan
- Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany
| | - Moritz Drefs
- Department of General, Visceral and Transplantation Surgery, University Hospital of Munich, Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany
| | - Tobias S Schiergens
- Department of General, Visceral and Transplantation Surgery, University Hospital of Munich, Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany
| | - Jutta Engel
- Munich Cancer Registry (MCR), Bavarian Cancer Registry - Regional Centre Munich (LGL) at the University Hospital of Munich, Institute for Medical Information Processing, Biometry, and Epidemiology (IBE), Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany
| | - Martin K Angele
- Department of General, Visceral and Transplantation Surgery, University Hospital of Munich, Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany
| | - Jens Werner
- Department of General, Visceral and Transplantation Surgery, University Hospital of Munich, Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany
| | - Markus Guba
- Department of General, Visceral and Transplantation Surgery, University Hospital of Munich, Ludwig-Maximilians-Universität München (LMU), Marchioninistr. 15, 81377 Munich, Germany
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Hartung F, Wang Y, Aronow B, Weber GF. A core program of gene expression characterizes cancer metastases. Oncotarget 2017; 8:102161-102175. [PMID: 29254233 PMCID: PMC5731943 DOI: 10.18632/oncotarget.22240] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Accepted: 08/31/2017] [Indexed: 11/25/2022] Open
Abstract
While aberrant expression or splicing of metastasis genes conveys to cancers the ability to break through tissue barriers and disseminate, the genetic basis for organ preference in metastasis formation has remained incompletely understood. Utilizing the gene expression profiles from 653 GEO datasets, we investigate whether the signatures by diverse cancers in various metastatic sites display common features. We corroborate the meta-analysis in a murine model. Metastases are generally characterized by a core program of gene expression that induces the oxidative metabolism, activates vascularization/tissue remodeling, silences extracellular matrix interactions, and alters ion homeostasis. This program distinguishes metastases from their originating primary tumors as well as from their target host tissues. Site-selectivity is accomplished through specific components that adjust to the target micro-environment. The same functional groups of gene expression programs are activated in the metastases of B16-F10 cells to various target organs. It remains to be investigated whether these genetic signatures precede implantation and thus determine organ preference or are shaped by the target site and are thus a consequence of implantation. Conceivably, chemotherapy of disseminated cancer might be more efficacious if selected to match the genetic makeup of the metastases rather than the organ of origin by the primary tumor.
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Affiliation(s)
- Franz Hartung
- University of Cincinnati Academic Health Center, Cincinnati, OH, USA
| | - Yunguan Wang
- Computational Medicine Center, Cincinnati Children's Hospital, Cincinnati, OH, USA
| | - Bruce Aronow
- Computational Medicine Center, Cincinnati Children's Hospital, Cincinnati, OH, USA
| | - Georg F Weber
- University of Cincinnati Academic Health Center, Cincinnati, OH, USA
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Kim HK, Cho JH, Lee HY, Lee J, Kim J. Pulmonary metastasectomy for colorectal cancer: How many nodules, how many times? World J Gastroenterol 2014; 20:6133-6145. [PMID: 24876735 PMCID: PMC4033452 DOI: 10.3748/wjg.v20.i20.6133] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2013] [Revised: 11/01/2013] [Accepted: 03/05/2014] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide, with 5%-15% of CRC patients eventually developing lung metastasis (LM). Despite doubts about the role of locoregional therapy in the management of systemic disease, many surgeons have performed pulmonary metastasectomy (PM) for CRC in properly selected patients. However, the use of pulmonary metastasectomy remains controversial due to the lack of randomized controlled studies. This article reviews the results of surgical treatment of pulmonary metastases for CRC, focusing on (1) current treatment guidelines and surgical techniques of PM in patients with LM from CRC; (2) outcomes of PM and its prognostic factors; and (3) controversial issues in PM, focusing on repeated metastasectomy, bilateral multiple metastases, and combined liver and lung metastasectomy.
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