| Objective Colon cancer is one of the common malignant tumors worldwide,endangering human life and health.Immunotherapy has become an important method for treating various tumors,but not all cancer patients can benefit from it,the efficacy of immunotherapy depends on the tumor microenvironment(TME).Based on the 165 novel cancer prediction genes(NCPGs)proposed by previous researchers that can interact with well-known cancer genes(such as TP53,BRCA1,and EP300),we used a single-factor Cox regression model to screen 29 NCPGs that have prognostic value in colon cancer,and comprehensively evaluated the relationship between 29 NCPGs and the prognosis,immune infiltration,and clinicopathological characteristics of patients with colon cancer by bioinformatics method.Methods Firstly,the transcriptome and partial clinical information of 1008 patients with colon cancer in TCGA-COAD and GESE39582 cohorts were collected,and the data were merged and processed by Perl software.Then,165 NCPGs were analyzed by single-factor Cox regression analysis,and 29 NCPGs with prognostic value were identified.Based on these 29 NCPGs,the patients with colon cancer were divided into two subtypes,we analyzed the clinicopathological characteristics,prognosis,signal pathway activation status,and TME cell infiltration characteristics of the two subtypes.Then,750 differentially expressed genes(DEGs)of two subtypes were identified by the "limma" R package,and 336 DEGs with prognostic value were identified by single-factor Cox regression analysis on 750 DEGs.Based on these 336 DEGs with prognostic value,the patients with colon cancer were divided into three gene clusters,and the clinicopathological characteristics,prognosis,signal pathway activation status,the expression of immune checkpoints,and the characteristics of TME cell infiltration of the three gene clusters were analyzed.Finally,we built a scoring system using the principal components analysis(PCA)method to score each colon cancer patient,divide the patients into the high NCPGscore group and the low NCPGscore group,and analyze the relationship between NCPGscore and survival,signal pathway activation status and TME cell infiltration characteristics of patients.The potential of NCPG in immunotherapy was evaluated by the correlation between NCPGscore with tumor mutation burden(TMB)and microsatellite instability(MSI).Results This study identified 29 NCPGs that can be used as prognostic indicators for patients with colon cancer.The functional enrichment analysis of 750 DEGs showed that29 NCPGs play a crucial role in the immune regulation of TME.Based on the expression of 336 DEGs with prognostic value,we divided the patients into three gene clusters.According to the comprehensive analysis results of gene cluster characteristics,most of the colon cancer patients in gene cluster A prefer the immune desert phenotype,characterized by low immune infiltration abundance.Gene cluster B is characterized by inherent immune infiltration and high genomic instability,most of the patients within this gene cluster prefer the immune inflamed phenotype,and gene cluster C is characterized by high expression of immune checkpoints,high activation of transforming growth factor-β(TGF-β),and most patients within the gene cluster prefer the immune excluded phenotype.Based on the scoring of two subtypes and three gene clusters,the results of survival analysis and immune infiltration evaluation combined with subtypes,gene cluster,and NCPGscore groups demonstrate that the NCPGScore has good predictive performance in survival and immune infiltration evaluation.By analyzing the correlation between NCPGscore with TMB,and MSI,we found that patients with high NCPGscore were more suitable for immunotherapy due to high TMB and microsatellite instability-high(MSI-H).Conclusion We identified 29 NCPGs that can be used as prognostic indicators for colon cancer patients,and the comprehensive analysis of 29 NCPGs revealed their impact on tumor microenvironment,clinicopathological characteristics,and prognosis in colon cancer patients.Assessing the NCPGscore of single tumor can enhance our understanding of the characteristics of TME infiltration,demonstrating the important clinical significance of 29 NCPGs in patients with colon cancer,which can help achieve immune classification of tumors in patients with colon cancer,and provide data reference for formulating more effective immunotherapy strategies for patients with colon cancer.Significance We identified 29 NCPGs that can be used as prognostic indicators for colon cancer patients.Our comprehensive analysis shows that NCPGscore can be an ideal predictor of the prognosis and immune therapy response of colon cancer patients.In summary,our research results provide certain data support and reference for achieving immune classification of colon cancer patients and screening cancer patients who are more likely to benefit from immunotherapy. |
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