Abstract
Background: Globally, colorectal cancer (CRC) is one of the most lethal malignant diseases. However, the currently approved therapeutic options for CRC failed to acquire satisfactory treatment efficacy. Tailoring therapeutic strategies for CRC individuals can provide new insights into personalized prediction approaches and thus maximize clinical benefits.Methods: In this study, a multi-step process was used to construct an immune-related genes (IRGs) based signature leveraging the expression profiles and clinical characteristics of CRC from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. An integrated immunogenomic analysis was performed to determine the association between IRGs with prognostic significance and cancer genotypes in the tumor immune microenvironment (TIME). Moreover, we performed a comprehensive in silico therapeutics screening to identify agents with subclass-specific efficacy.Results: The established signature was shown to be a promising biomarker for evaluating clinical outcomes in CRC. The immune risk score as calculated by this classifier was significantly correlated with over-riding malignant phenotypes and immunophenotypes. Further analyses demonstrated that CRCs with low immune risk scores achieved better therapeutic benefits from immunotherapy, while AZD4547, Cytochalasin B and S-crizotinib might have potential therapeutic implications in the immune risk score-high CRCs.Conclusions: Overall, this IRGs-based signature not only afforded a useful tool for determining the prognosis and evaluating the TIME features of CRCs, but also shed new light on tailoring CRCs with precise treatment.
Highlights
Colorectal cancer (CRC) is the third most frequently occurring cancer and the second leading cause of cancer-related deaths worldwide in 2018 [1]
Through systematic in silico analysis based on the constructed signature, we discovered that the immune-related genes (IRGs) risk score for colorectal cancer (CRC) was associated with overall survival (OS), clinicopathological factors, and immunophenotypic characteristics
The formula for calculating risk score is: Risk score = 0.139 х ExpFABP4 + 0.176 х ExpAMH + 0.207 х ExpGRP + 0.211 х ExpINHBB 0.691 х ExpNRG1 + 0.274 х ExpUCN + 0.366 х ExpMC1R. Among these IRGs, neuregulin 1 (NRG1) exhibited a negative coefficient, implying that it could be considered as a protective factor for CRCs; on the contrary, fatty acid binding protein 4 (FABP4), Anti-Müllerian hormone (AMH), gastrin-releasing peptide (GRP), inhibin subunit beta B (INHBB), UCN, and melanocortin-1 receptor (MC1R) possess positive coefficients, implying poor prognoses in CRCs with overexpression of these six genes
Summary
Colorectal cancer (CRC) is the third most frequently occurring cancer and the second leading cause of cancer-related deaths worldwide in 2018 [1]. Several other biomarkers of potential response have been demonstrated, including high tumor mutation load [17, 18], high immunoscore [19, 20], and POLE mutation [21, 22] These biomarkers that guided the use of ICIs in patients with CRC are not always consistent in clinical practice. Further analyses demonstrated that CRCs with low immune risk scores achieved better therapeutic benefits from immunotherapy, while AZD4547, Cytochalasin B and Scrizotinib might have potential therapeutic implications in the immune risk score-high CRCs. Conclusions: Overall, this IRGs-based signature afforded a useful tool for determining the prognosis and evaluating the TIME features of CRCs, and shed new light on tailoring CRCs with precise treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
