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Multi-omics analysis of the Indian ovarian cancer cohort revealed histotype-specific mutation and gene expression patterns
Introduction: In India, OVCa is women’s third most common and lethal cancer type, accounting for 6.7% of observed cancer incidences. The contribution of somatic mutations, aberrant expression of gene and splice forms in determining the cell fate, gene networks, tumour-specific variants, and the role...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117685/ https://www.ncbi.nlm.nih.gov/pubmed/37091785 http://dx.doi.org/10.3389/fgene.2023.1102114 |
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author | Mhatre, Anisha Koroth, Jinsha Manjunath, Meghana Kumar S, Sandeep Gawari, Ramesh Choudhary, Bibha |
author_facet | Mhatre, Anisha Koroth, Jinsha Manjunath, Meghana Kumar S, Sandeep Gawari, Ramesh Choudhary, Bibha |
author_sort | Mhatre, Anisha |
collection | PubMed |
description | Introduction: In India, OVCa is women’s third most common and lethal cancer type, accounting for 6.7% of observed cancer incidences. The contribution of somatic mutations, aberrant expression of gene and splice forms in determining the cell fate, gene networks, tumour-specific variants, and the role of immune fraction infiltration have been proven essential in understanding tumorigenesis. However, their interplay in OVCa in a histotype-specific manner remains unclear in the Indian context. In the present study, we aimed to unravel the Indian population histotype-specific exome variants, differentially expressed gene modules, splice events and immune profiles of OVCa samples. Methods: We analysed 10 tumour samples across 4 ovarian cancer histotypes along with 2 normal patient samples. This included BCFtool utilities and CNVkit for exome, WGCNA and DESeq2 for obtaining differential module hub genes and dysregulated miRNA targets, CIBERSORTx for individual immune profiles and rMATS for tumour specific splice variants. Result: We identified population-specific novel mutations in Cancer Gene Census Tier1 and Tier2 genes. MUC16, MUC4, CIITA, and NCOR2 were among the most mutated genes, along with TP53. Transcriptome analysis showed significant overexpression of mutated genes MUC16, MUC4, and CIITA, whereas NCOR2 was downregulated. WGCNA revealed histotype-specific gene hubs and networks. Among the significant pathways, alteration in the immune system was one of the pathways, and immune profiling using CIBERSORTx revealed histotype-specific immune cell fraction. miRNA analysis revealed miR-200 family, miR-200a and miR-429 were upregulated in HGSOCs.Splice factor abrasion caused splicing perturbations, with the most abundant alternative splice event being exon skipping and the most spliced gene, SNHG17. Pathway analysis of spliced genes revealed translational elongation and Base excision repair as the pathways altered in OVCa. Conclusion: Integrated exome, transcriptome, and splicing patterns revealed different population-specific molecular signatures of ovarian cancer histotypes in the Indian Cohort. |
format | Online Article Text |
id | pubmed-10117685 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-101176852023-04-21 Multi-omics analysis of the Indian ovarian cancer cohort revealed histotype-specific mutation and gene expression patterns Mhatre, Anisha Koroth, Jinsha Manjunath, Meghana Kumar S, Sandeep Gawari, Ramesh Choudhary, Bibha Front Genet Genetics Introduction: In India, OVCa is women’s third most common and lethal cancer type, accounting for 6.7% of observed cancer incidences. The contribution of somatic mutations, aberrant expression of gene and splice forms in determining the cell fate, gene networks, tumour-specific variants, and the role of immune fraction infiltration have been proven essential in understanding tumorigenesis. However, their interplay in OVCa in a histotype-specific manner remains unclear in the Indian context. In the present study, we aimed to unravel the Indian population histotype-specific exome variants, differentially expressed gene modules, splice events and immune profiles of OVCa samples. Methods: We analysed 10 tumour samples across 4 ovarian cancer histotypes along with 2 normal patient samples. This included BCFtool utilities and CNVkit for exome, WGCNA and DESeq2 for obtaining differential module hub genes and dysregulated miRNA targets, CIBERSORTx for individual immune profiles and rMATS for tumour specific splice variants. Result: We identified population-specific novel mutations in Cancer Gene Census Tier1 and Tier2 genes. MUC16, MUC4, CIITA, and NCOR2 were among the most mutated genes, along with TP53. Transcriptome analysis showed significant overexpression of mutated genes MUC16, MUC4, and CIITA, whereas NCOR2 was downregulated. WGCNA revealed histotype-specific gene hubs and networks. Among the significant pathways, alteration in the immune system was one of the pathways, and immune profiling using CIBERSORTx revealed histotype-specific immune cell fraction. miRNA analysis revealed miR-200 family, miR-200a and miR-429 were upregulated in HGSOCs.Splice factor abrasion caused splicing perturbations, with the most abundant alternative splice event being exon skipping and the most spliced gene, SNHG17. Pathway analysis of spliced genes revealed translational elongation and Base excision repair as the pathways altered in OVCa. Conclusion: Integrated exome, transcriptome, and splicing patterns revealed different population-specific molecular signatures of ovarian cancer histotypes in the Indian Cohort. Frontiers Media S.A. 2023-04-06 /pmc/articles/PMC10117685/ /pubmed/37091785 http://dx.doi.org/10.3389/fgene.2023.1102114 Text en Copyright © 2023 Mhatre, Koroth, Manjunath, Kumar S, Gawari and Choudhary. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Mhatre, Anisha Koroth, Jinsha Manjunath, Meghana Kumar S, Sandeep Gawari, Ramesh Choudhary, Bibha Multi-omics analysis of the Indian ovarian cancer cohort revealed histotype-specific mutation and gene expression patterns |
title | Multi-omics analysis of the Indian ovarian cancer cohort revealed histotype-specific mutation and gene expression patterns |
title_full | Multi-omics analysis of the Indian ovarian cancer cohort revealed histotype-specific mutation and gene expression patterns |
title_fullStr | Multi-omics analysis of the Indian ovarian cancer cohort revealed histotype-specific mutation and gene expression patterns |
title_full_unstemmed | Multi-omics analysis of the Indian ovarian cancer cohort revealed histotype-specific mutation and gene expression patterns |
title_short | Multi-omics analysis of the Indian ovarian cancer cohort revealed histotype-specific mutation and gene expression patterns |
title_sort | multi-omics analysis of the indian ovarian cancer cohort revealed histotype-specific mutation and gene expression patterns |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10117685/ https://www.ncbi.nlm.nih.gov/pubmed/37091785 http://dx.doi.org/10.3389/fgene.2023.1102114 |
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