Uncovering Potential Therapeutic Targets in Colorectal Cancer by Deciphering Mutational Status and Expression of

Otília Menyhart1,2, Tatsuhiko Kakisaka3,4, Lőrinc Sándor Pongor1,2

  • 12nd Department of Pediatrics, Semmelweis University, Tűzoltó utca 7-9, H-1094 Budapest, Hungary.

Cancers
|July 25, 2019
PubMed
Abstract

Insights

This study identified 37 potentially druggable genes in colorectal cancer (CRC) by analyzing mutation-associated gene expression. These findings may help stratify patients for targeted therapies and improve CRC treatment outcomes.

Area of Science:

  • Genomics
  • Oncology
  • Translational Medicine

Background:

  • Colorectal cancer (CRC) has numerous driver mutations, but their therapeutic relevance is unclear.
  • Investigating downstream signaling pathway effects of driver mutations can reveal therapeutic targets.
  • This study aimed to identify differentially expressed genes linked to driver mutations as potential drug targets.

Purpose of the Study:

  • To identify potentially actionable drug targets in colorectal cancer.
  • To correlate gene expression changes with specific driver mutations in CRC.
  • To discover genes associated with patient survival outcomes in CRC.

Main Methods:

  • Somatic mutation and gene expression data from 582 CRC patients were analyzed.
  • Gene expression levels in wild-type versus mutant cases were compared using the Mann-Whitney test.
  • Survival analysis and druggability filters were applied to identify and validate potential therapeutic targets.

Main Results:

  • 426 disruptive mutation-associated upregulated genes were identified in CRC.
  • 95 of these genes correlated with worse recurrence-free survival (RFS).
  • 37 potentially actionable targets were revealed, with specific genes like DUSP4, BMP4, TRIB2, and VSIG4 validated in patient specimens.

Conclusions:

  • Potentially druggable genes were identified in colorectal cancer.
  • The identified mutations and associated genes can facilitate future patient stratification for targeted therapy.
  • This research provides a foundation for developing novel targeted treatments for CRC.

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