m6A-related lncRNA-based immune infiltration characteristics and prognostic model in colonic adenocarcinoma

Background: Colonic adenocarcinoma (COAD) is a common gastrointestinal tract tumor, and its occurrence and progression are usually associated with genomic instability, tumor suppressor gene and oncogene mutations, and tumor mutational load.The biological importance of RNA N6-methyladenosine (m6A) modification and long non-coding RNA (lncRNA) expression in tumorigenesis and progression has been demonstrated. However, the regulatory role of m6A ‐ associated lncRNAs in the tumor microenvironment (TME) and the stratification of prognosis and immunotherapy have not been determined.Methods: We screened 43 prognostic lncRNAs linked to m6A and conducted consistent molecular typing of COAD using consensus clustering. The ssGSEA algorithm and the ESTIMATE algorithm were employed to assess the immune characteristics describing the different subgroups. Covariation between methylation-related prognostic lncRNAs was then eliminated by least absolute shrinkage and selection operator (Lasso) Cox regression. A nomogram was created and evaluated by combining the methylation-related prognostic lncRNA model with other clinical factors. And, the relationship between prognostic model grouping and microsatellite instability (MSI), immunophenotype score (IPS) and tumor mutation burden (TMB) was further validated using R language. Finally we used the linkage map (CMAP) to filter sensitive medicines to suppress the expression of high-risk genes.Results: Three separate m6A-associated lncRNA modes were discovered in 446 COAD specimens with different clinical endpoints and biological status. Risk scores were constructed based on m6A-associated lncRNA signature genes. Patients with lesser risk scores demonstrated superior immunotherapy response and clinical benefit. Further profiling suggested that lesser risk scores were also correlated with higher IPS scores, tumor mutation burden, and mutation rates in significant mutated genes (SMGs) (e.g., FAT4 and MUC16). Piperidolate, quinostatin, and mecamylamin were then screened for their ability to suppress expression of high-risk genes in the model.Conclusions: Quantitative assessment of m6A-associated lncRNAs in single tumors is expected to enhance our comprehension of the TME profile. M6A-associated lncRNAs constructed a prognostic model that facilitates prognosis and immunotherapy stratification in COAD patients, and based on the model we screened three drugs with potential therapeutic value.