Genomic landscape and expression profile of consensus molecular subtype four of colorectal cancer

Yujie Lu1, Dingyi Gu1, Chenyi Zhao1

  • 1Department of Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.

PubMed
Abstract

Insights

The CMS4 subtype of colorectal cancer (CRC) shows poorer survival and limited treatment options. This study identified key mutations and immune cell profiles in CMS4 CRC, offering new therapeutic targets.

Area of Science:

  • Oncology
  • Genomics
  • Immunology

Background:

  • The CMS4 subtype of colorectal cancer (CRC) is characterized by poor prognosis and a lack of effective therapies.
  • Identifying molecular and immunological features of CMS4 CRC is crucial for developing targeted treatments.

Purpose of the Study:

  • To investigate the genomic landscape, gene expression profiles, and tumor microenvironment of the CMS4 CRC subtype.
  • To identify potential therapeutic targets and biomarkers for CMS4 CRC.

Main Methods:

  • Whole exome sequencing and RNA sequencing were performed on 24 CRC patients.
  • Intratumoral heterogeneity was quantified using the Mutational Allelic Burden (MATH) score.
  • Pathway analysis, gene enrichment analysis, and immune cell infiltration analysis were conducted.

Main Results:

  • CMS4 patients exhibited worse progression-free survival (PFS) compared to CMS2/3 subtypes.
  • Commonly mutated genes in CMS4 CRC included CTNNB1 (Wnt pathway) and CCNE1 (cell cycle pathway).
  • CMS4 tumors showed lower MATH scores, enrichment of M2 macrophages, and an immunosuppressive tumor microenvironment.

Conclusions:

  • The CMS4 subtype of CRC presents distinct genomic alterations and a unique immune microenvironment.
  • These findings provide novel insights for developing targeted therapeutic strategies for CMS4 CRC patients.

Related Concept Videos