| BackgroundColorectal cancer(CRC)is the third most common malignant tumor in the world and the major cause of malignant cancer in China.The incidence of the disease tends to be younger,and the pathogenesis is complex involving the regulation of genetics,epigenetics,tumor microenvironment and other factors.Facing the complex formation mechanism,it is of great clinical significance to find new prognostic markers and therapeutic targets for colon cancer.N6-methyladenosine(m6A)is a novel epigenetic modification which affects almost every step of mRNA metabolism including mRNA stability,RNA folding,splicing,translation and other RNA modifications.Long non-coding RNA(lncRNA)refers to a class of long RNA molecules with a transcription length of more than 200 nucleosides with no protein-coding function.Widely involved in the body’s pathophysiological process,lncRNA regulates the expression of related genes at various levels such as chromosomal modification,transcriptional activation and silencing,nuclear transformation and epigenetic inheritance.However,the role of m6A regulatory factor in the dysregulation of lncRNA in cancers remains unclear,and studies on how m6A modification promotes the occurrence and development of lncRNA-dependent colon cancer are also limited.Therefore,studying the abnormal expression of m6A-related IlncRNA may have prognostic value for colon cancer patients,and understanding how m6A modification of lncRNA is involved in the occurrence of colon cancer will help identify new therapeutic targets and biomarkers.This research explored the expression and prognostic value of m6A-related lncRNA in colon cancer,and studied its relationship with clinical characteristics and tumor immune microenvironment of colon cancer patients.MethodFirstly,RNA sequencing data and relevant clinical information of CRC samples were downloaded from TCGA database.Then,the expression level of m6A-related lncRNA was extracted,and the co-expression network of m6A-related lncRNA was constructed by co-expression analysis method.Prognostic m6A lncRNA was obtained by univariate Cox analysis.Next,consistent cluster analysis was used to determine whether the expression of 23 m6A methylation regulators of lncRNA in tumor tissues could be classified into different types.K-M survival curve was used to evaluate the relationship between tumor typing and prognosis and to analyze the correlation between tumor classification and clinical features as well as the expression of genes associated with immune checkpoint inhibitors in different tumor types.To analyze the relationship between tumor classification and immune cell infiltration,the "Estimate"R package was used to calculate the stromal and immune cell ratios separately to derive tumor purity for each patient,thus determining stromal and immune cell ratios between groups.CIBERSORT algorithm was used to investigate the composition of infiltrating immune cells in each group,and GSEA method was used to quantify the degree of tumor immune invasion.The risk prognostic model of m6A lncRNA was established by Lasso Cox regression analysis.All samples were divided into the training set and the verification set by randomization grouping.Risk scores were calculated for each group,and all samples were divided into high-risk and low-risk groups according to the median risk score.The robustness of the model was evaluated by K-M survival curve and ROC curve in the training set and validation set,respectively.Independent prognostic analysis was performed to verify the applicability of the model via subgroups.The degree of tumor immune infiltration was assessed by ssGESA.Finally,the survival rate of colon cancer patients in the TCGA cohort was estimated using constructed nomogram.ResultsIn this research,differences were found between m6A-related lncRNA and colon cancer tumor tissues and adjacent tissues.Univariate Cox regression analysis and Lasso Cox regression analysis finally screened 8 m6A-related lncRNA for the construction of the prognostic model of colon cancer.Independent prognostic analysis showed that risk score was an independent prognostic factor for overall survival(p<0.001).Multiple ROC curve analysis verified that the risk model could better predict the prognosis of patients.The risk model constructed by 8 m6A-related lncRNA in colon cancer tissue has good predictive value and is closely related to clinical characteristics and is an independent risk factor for overall survival of patients.And immune-related pathways were significantly enriched in enrichment analysis.ConclusionThe expression characteristics of m6A-associated lncRNA in colon cancer are correlated with clinicopathological features.In this study,a new prognostic model of m6A-associated lncRNA in colon cancer was established,which can be well used to predict the overall survival rate of colon cancer patients.M6A-associated lncRNA may be a promising therapeutic target and biomarker for colon cancer. |
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