Exploring Cancer Dependency Map genes and immune subtypes in colon cancer, in which contributes to colon cancer progression.

BACKGROUND

Tumour-dependent genes identified in CRISPR-Cas9 screens have been widely reported in Cancer Dependency Maps (CDMs). CDM-derived tumour-dependent genes play an important role in tumorigenesis and progression; however, they have not been investigated in colon cancer (CC).

METHODS

CDM genes overexpressed in CC were identified from the TCGA-COAD dataset and CDM platform. A CDM signature and prognostic nomogram were constructed by Lasso Cox regression and multivariate Cox analyses. A weighted correlation network analysis (WGCNA) and consensus clustering were used to define coexpressed genes with CDM risk scores and to determine two new immune subtypes. A comprehensive investigation was performed between the two subtypes and immune regulation, the immune microenvironment and the impact of immunotherapy.

RESULTS

First, 1304 overexpressed CDM genes were identified. Then, a CDM signature with five cancer-dependent genes ( and ) and a prognostic nomogram were constructed, and they demonstrated robust predictive performance and a close relationship with clinical characteristics in different CC datasets. Patients with high CDM risk scores showed worse survival outcome and weaker response to chemotherapy. Additionally, genes were oncogenes that affected the CC cell cycle, according to cell functional experiments that involved the suppression of the gene. Furthermore, WGCNA and consensus clustering were used to define coexpressed genes with CDM risk scores and to determine two new immune subtypes. Finally, systematic investigations were conducted with the relationship between the CDM subtypes and immune regulation.

CONCLUSIONS

This study constructed a CDM signature consisting of five risk genes that predict survival in CC patients. In addition, the immune subtypes provided valuable insights into immunotherapy for CC patients. , as an oncogene, is independent prognostic factors for CC, and contributes to CC progression.