Abstract
BackgroundDespite 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.MethodsIRGs 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.ResultsThe 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.ConclusionThe immune-related six-gene signature is a reliable prognostic indicator for CRC patients and could provide insight for personalized cancer management.
Highlights
Colorectal cancer (CRC) is the third most common malignant tumor worldwide and ranks second in tumor-related deaths (Bray et al, 2018)
To filter genes that actively participate in immune activity, a third comprehensive data set of immune genes was acquired from the Immunology Database and Analysis Portal database (ImmPort
As some genes showing no expression value in the above three gene expression profiles, a panel of 1,684 expressing immune-related gene (IRG) was further selected for survival analysis (Supplementary Table S1)
Summary
Colorectal cancer (CRC) is the third most common malignant tumor worldwide and ranks second in tumor-related deaths (Bray et al, 2018). Despite recent advancements in chemo-regimens and clinical management, the overall survival of CRC remains unsatisfactory: The 5 years overall survival is just over 50% (Frampton and Houlston, 2017). There is great heterogeneity in individuals regarding tumor development and in the response to uniform treatment: In those receiving surgeries, while some enjoyed disease-free survival, many suffered from tumor recurrence (Stelzner et al, 2019). Despite recent advance in immune therapy, great heterogeneity exists in the outcomes of colorectal cancer (CRC) patients. 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
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