Novel MicroRNA-Regulated Transcript Networks Are Associated with Chemotherapy Response in Ovarian Cancer

Abstract

High-grade serous ovarian cancer (HGSOC) is a highly lethal gynecologic cancer, in part due to resistance to platinum-based chemotherapy reported among 20% of patients. This study aims to generate novel hypotheses of the biological mechanisms underlying chemotherapy resistance, which remain poorly understood. Differential expression analyses of mRNA- and microRNA-sequencing data from HGSOC patients of The Cancer Genome Atlas identified 21 microRNAs associated with angiogenesis and 196 mRNAs enriched for adaptive immunity and translation. Coexpression network analysis identified three microRNA networks associated with chemotherapy response enriched for lipoprotein transport and oncogenic pathways, as well as two mRNA networks enriched for ubiquitination and lipid metabolism. These network modules were replicated in two independent ovarian cancer cohorts. Moreover, integrative analyses of the mRNA/microRNA sequencing and single-nucleotide polymorphisms (SNPs) revealed potential regulation of significant mRNA transcripts by microRNAs and SNPs (expression quantitative trait loci). Thus, we report novel transcriptional networks and biological pathways associated with resistance to platinum-based chemotherapy in HGSOC patients. These results expand our understanding of the effector networks and regulators of chemotherapy response, which will help to improve the management of ovarian cancer.

Repopulated spinal cord microglia exhibit a unique transcriptome and contribute to pain resolution

“…WGCNA is a powerful technique that has historically been applied to population-level studies of publicly available datasets. 40 , 41 Our study is unique in applying WGCNA in the context of pain transcriptomic analysis of microglia. Using this in-depth, unbiased approach, we identified both sex-dependent and independent microglial transcriptional signatures related to the uninjured, injured, or pain-resolved states.…”

Newly repopulated spinal cord microglia exhibit a unique transcriptome and correlate with pain resolution

“…WGCNA is a powerful technique that has historically been applied to population-level studies of publicly available datasets. (44, 45) Our study is unique in applying WGCNA in the context of pain transcriptomic analysis of microglia. Using this in-depth, unbiased approach, we identify both sex-dependent and independent microglial transcriptional signatures related to the uninjured, injured, or pain-resolved states.…”

“…WGCNA is a powerful technique that has historically been applied to population-level studies of publicly available datasets. (44,45) Our study is unique in applying WGCNA in the context of pain transcriptomic analysis of microglia.…”

The CircaHealth CircaPain study protocol: A longitudinal multi-site study of the chronobiological control of chronic pain

“…For example, we will evaluate, align, and assemble raw RNA sequencing reads with FastQC(37), Hisat2(38), and StringTie(39), as appropriate. Comparative bioinformatics analysis can then be used to identify genes, transcripts, proteins, and pathways of interest by mining weighted gene coexpression network analysis (WGCNA), as previously done(40-46).…”