A comprehensive genomic meta-analysis identifies confirmatory role ofOBSCNgene in breast tumorigenesis

Abstract

The giant multifunctional protein “OBSCURIN” is encoded by OBSCN gene and is mostly expressed in cardiac and other skeletal muscles responsible for myofibrils organization. Loss of OBSCURIN affects the entire downstream pathway proteins vital for various cellular functions including cell integration and cell adhesion. The OBSCN gene mutations are more frequently observed in various muscular diseases, and cancers. Nevertheless, the direct role of OBSCN in tumorigenesis remains elusive. Interestingly, in clinical breast cancer samples a significant number of function changing mutations have been identified in OBSCN gene. In this study, we identified a significant role of OBSCN by conducting an integrative analysis of copy number alterations, functional mutations, gene methylation and expression data from various BRCA cancer projects data available on cBioPortal and TCGA firebrowse portal. Finally, we carried out genetic network analysis, which revealed that OBSCN gene plays a significant role in GPCR, RAS, p75 or Wnt signaling pathways. Similarly, OBSCN gene interacts with many cancer-associated genes involved in breast tumorigenesis. The OBSCN gene probably regulates breast cancer progression and metastasis and the prognostic molecular signatures such as copy number alterations and gene expression of OBSCN may serve as a tool to identify breast tumorigenesis and metastasis.

Pan-Cancer Analysis of Human Kinome Gene Expression and Promoter DNA Methylation Identifies Dark Kinase Biomarkers in Multiple Cancers

“…We found five CpG probes mapped to OBSCN gene significant in survival in KIRP, UCEC and UVM cancers. OBSCN gene has been reported to interact with many cancer-associated genes involved in breast tumorigenesis [ 39 ]. The survival analysis results based on expression and methylation are given in Supplementary Tables S5 and S6 respectively.…”

Discovering mutated driver genes through a robust and sparse co-regularized matrix factorization framework with prior information from mRNA expression patterns and interaction network

“…Gene USH2A is another genes in BRCA results of our model, and USH2A mutations have been identified highlighting the molecular diversity observed in triple-negative breast cancers by a recent research [ 75 ]. The OBSCN is also detected in BRCA results by our model, which is likely to regulate breast cancer progression and metastasis and the prognostic molecular signatures [ 76 ].…”

Multi-omics Data Integration, Interpretation, and Its Application

“…The ease of use and wide spectrum of tools in this portal have resulted in its popularity among researchers. 82,83 For instance, Rajendran et al 92 showed the role of OBSCRN gene in breast cancer tumorigenesis by integrating copy number, mutation, methylation, and gene expression data from cBioPortal.…”