Identification of an Immune-Related Gene Signature to Improve Prognosis Prediction in Colorectal Cancer Patients

Siqi Dai; Shuang Xu; Yao Ye; Kefeng Ding

doi:10.3389/fgene.2020.607009

Identification of an Immune-Related Gene Signature to Improve Prognosis Prediction in Colorectal Cancer Patients

Front Genet. 2020 Dec 4:11:607009. doi: 10.3389/fgene.2020.607009. eCollection 2020.

Authors

Siqi Dai^{1

2}, Shuang Xu³, Yao Ye^{1

2}, Kefeng Ding^{1

2}

Affiliations

¹ Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Zhejiang University Cancer Center, Hangzhou, China.
³ Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.

Abstract

Background: Despite recent advance in immune therapy, great heterogeneity exists in the outcomes of colorectal cancer (CRC) patients. In this study, we aimed to analyze the immune-related gene (IRG) expression profiles from three independent public databases and develop an effective signature to forecast patient's prognosis.

Methods: IRGs were collected from the ImmPort database. The CRC dataset from The Cancer Genome Atlas (TCGA) database was used to identify a prognostic gene signature, which was verified in another two CRC datasets from the Gene Expression Omnibus (GEO). Gene function enrichment analysis was conducted. A prognostic nomogram was built incorporating the IRG signature with clinical risk factors.

Results: The three datasets had 487, 579, and 224 patients, respectively. A prognostic six-gene-signature (CCL22, LIMK1, MAPKAPK3, FLOT1, GPRC5B, and IL20RB) was developed through feature selection that showed good differentiation between the low- and high-risk groups in the training set (p < 0.001), which was later confirmed in the two validation groups (log-rank p < 0.05). The signature outperformed tumor TNM staging for survival prediction. GO and KEGG functional annotation analysis suggested that the signature was significantly enriched in metabolic processes and regulation of immunity (p < 0.05). When combined with clinical risk factors, the model showed robust prediction capability.

Conclusion: The immune-related six-gene signature is a reliable prognostic indicator for CRC patients and could provide insight for personalized cancer management.

Keywords: colorectal cancer; gene signature; immunity; prediction model; prognosis.