Multi-omics analysis of the Indian ovarian cancer cohort revealed histotype-specific mutation and gene expression patterns

Abstract

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.

Current strategies for early epithelial ovarian cancer detection using miRNA as a potential tool

“…Multi omics approach integrates various datasets based on transcriptomics, metabolomics, microarray, genomics and proteomics studies and is studied by biological scientists to extract the required information of a biological system or a cell and describe the disease profile. Analyzing miRNA data by multi omics approach based on miRNA sequencing, the Indian cohort’s HGSOC samples displayed significant expression levels of the miR-200 and miR-1269a families ( Mhatre et al, 2023 ). Their results displayed population-specific gene expression patterns and molecular signatures based on the histotypes found in the Indian cohort.…”