Abstract
BackgroundColon adenocarcinoma (COAD) can be divided into left-sided and right-sided COAD (LCCs and RCCs, respectively). They have unique characteristics in various biological aspects, particularly immune invasion and prognosis. The purpose of our study was to develop a prognostic risk scoring model (PRSM) based on differentially expressed immune-related genes (IRGs) between LCCs and RCCs, therefore the prognostic key IRGs could be identified.MethodsThe gene sets and clinical information of COAD patients were derived from TCGA and GEO databases. The comparison of differentially expressed genes (DEGs) of LCCs and RCCs were conducted with appliance of “Limma” analysis. The establishment about co-expression modules of DEGs related with immune score was conducted by weighted gene co-expression network analysis (WGCNA). Furthermore, we screened the module genes and completed construction of gene pairs. The analysis of the prognosis and the establishment of PRSM were performed with univariate- and lasso-Cox regression. We employed the PRSM in the model group and verification group for the purpose of risk group assignment and PRSM accuracy verification. Finally, the identification of the prognostic key IRGs was guaranteed by the adoption of functional enrichment, “DisNor” and protein-protein interaction (PPI).ResultsA total of 215 genes were screened out by differential expression analysis and WGCNA. A PRSM with 16 immune-related gene pairs (IRGPs) was established upon the genes pairing. Furthermore, we confirmed that the risk score was an independent factor for survival by univariate- and multivariate-Cox regression. The prognosis of high-risk group in model group (P < 0.001) and validation group (P = 0.014) was significantly worse than that in low-risk group. Treg cells (P < 0.001) and macrophage M0 (P = 0.015) were highly expressed in the high-risk group. The functional analysis indicated that there was significant up-regulation with regard of lymphocyte and cytokine related terms in low-risk group. Finally, we identified five prognostic key IRGs associated with better prognosis through PPI and prognostic analysis, including IL2RB, TRIM22, CIITA, CXCL13, and CXCR6.ConclusionThrough the analysis and screening of the DEGs between LCCs and RCCs, we constructed a PRSM which could predicate prognosis of LCCs and RCCs, and five prognostic key IRGs were identified as well. Therefore, the basis for identifying the benefits of immunotherapy and immunomodulatory was built.
Highlights
With year-by-year increase of colorectal cancer (CRC) incidence worldwide, CRC is considered as one of the main causes of death due to cancer [1]
The CRCs are mainly distinguished with embryonic origin, there are great significances existing between the left-sided colon cancers (LCCs) and right-sided colon cancers (RCCs) in various clinical aspects, such as metastasis tendency, survival and prognosis, chemotherapy drugs, immunotherapy, and sensitivity of molecularly targeted drugs, etc. [5,6,7]
It was found by other studies that biomarkers for the prognosis of colon cancer, including microsatellite instability-high [23], CpG island methylator phenotype-high [24], RAS [25], phosphoinositide 3-kinase pathway [26], and BRAF mutations [24]
Summary
With year-by-year increase of colorectal cancer (CRC) incidence worldwide, CRC is considered as one of the main causes of death due to cancer [1]. Cancers located in the colon can be divided into left-sided colon cancers (LCCs) and right-sided colon cancers (RCCs) as per different definitions [2,3,4]. The difference in prognosis makes colon cancer sidedness a criterion for predicting prognosis of all clinical stages [8]. These differences have given us incentives to gain deep understanding of the molecular biological mechanism. Colon adenocarcinoma (COAD) can be divided into left-sided and rightsided COAD (LCCs and RCCs, respectively). They have unique characteristics in various biological aspects, immune invasion and prognosis. The purpose of our study was to develop a prognostic risk scoring model (PRSM) based on differentially expressed immune-related genes (IRGs) between LCCs and RCCs, the prognostic key IRGs could be identified
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