An Integrative Systems Biology Approach Identifies Molecular Signatures Associated with Gallbladder Cancer Pathogenesis

Abstract

Gallbladder cancer (GBC) has a lower incidence rate among the population relative to other cancer types but is a major contributor to the total number of biliary tract system cancer cases. GBC is distinguished from other malignancies by its high mortality, marked geographical variation and poor prognosis. To date no systemic targeted therapy is available for GBC. The main objective of this study is to determine the molecular signatures correlated with GBC development using integrative systems level approaches. We performed analysis of publicly available transcriptomic data to identify differentially regulated genes and pathways. Differential co-expression network analysis and transcriptional regulatory network analysis was performed to identify hub genes and hub transcription factors (TFs) associated with GBC pathogenesis and progression. Subsequently, we assessed the epithelial-mesenchymal transition (EMT) status of the hub genes using a combination of three scoring methods. The identified hub genes including, CDC6, MAPK15, CCNB2, BIRC7, L3MBTL1 were found to be regulators of cell cycle components which suggested their potential role in GBC pathogenesis and progression.

MAP Kinase and mammalian target of rapamycin are main pathways of gallbladder carcinogenesis: Results from bioinformatic analysis of Next Generation Sequencing data from a hospital-based cohort

“…The use of other approaches, such as immunotherapy, hormone therapy, and targeted therapy, is mostly experimental, with a slight improvement in progression-free survival with no benefit in overall survival (22). With the advent of advanced methods such as whole-genome sequencing (WGS) using NGS or microarray platforms, the origin of genomic research has expanded, and newer approaches are being identified (23). This has also helped me understand the molecular mechanisms and prediction of treatment response and outcome.…”