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

Yujie Lu; Dingyi Gu; Chenyi Zhao; Ying Sun; Wenjing Li; Lulu He; Xiaoyan Wang; Zhongyang Kou; Jiang Su; Feng Guo

doi:10.3389/fimmu.2023.1160052

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

Front Immunol. 2023 Jun 19:14:1160052. doi: 10.3389/fimmu.2023.1160052. eCollection 2023.

Authors

Yujie Lu¹, Dingyi Gu¹, Chenyi Zhao¹, Ying Sun¹, Wenjing Li², Lulu He¹, Xiaoyan Wang¹, Zhongyang Kou³, Jiang Su³, Feng Guo¹

Affiliations

¹ Department of Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.
² Department of Clinical Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.
³ Department of General Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.

Abstract

Background: Compared to other subtypes, the CMS4 subtype is associated with lacking of effective treatments and poorer survival rates.

Methods: A total of 24 patients with CRC were included in this study. DNA and RNA sequencing were performed to acquire somatic mutations and gene expression, respectively. MATH was used to quantify intratumoral heterogeneity. PPI and survival analyses were performed to identify hub DEGs. Reactome and KEGG analyses were performed to analyze the pathways of mutated or DEGs. Single-sample gene set enrichment analysis and Xcell were used to categorize the infiltration of immune cells.

Results: The CMS4 patients had a poorer PFS than CMS2/3. CTNNB1 and CCNE1 were common mutated genes in the CMS4 subtype, which were enriched in Wnt and cell cycle signaling pathways, respectively. The MATH score of CMS4 subtype was lower. SLC17A6 was a hub DEG. M2 macrophages were more infiltrated in the tumor microenvironment of CMS4 subtype. The CMS4 subtype tended to have an immunosuppressive microenvironment.

Conclusion: This study suggested new perspectives for exploring therapeutic strategies for the CMS4 subtype CRC.

Keywords: colorectal cancer; consensus molecular subtype; gene expression; genomic mutations; tumor immune microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Colorectal Neoplasms* / pathology
Genomics
Humans
Macrophages / metabolism
Survival Analysis
Treatment Outcome
Tumor Microenvironment / genetics

Grants and funding

This study was funded by grants from Suzhou Municipal Science and Technology Bureau (Grant Number SKY2022006, SLJ202011 and SLT201959), Jiangsu Commission of Health (Grant Number M2020043) and China Digestive Tumor Clinical Research Public Welfare Project (Grant Number P014-038).