AbstractBackgroundThe current study probed prognosis‐related potential for m6A‐related lncRNAs signatures within colon tumor immune microenvironment (TIM).MethodsAfter downloading transcriptomic datasets for colon cancer (CC) patients from The Cancer Genome Atlas (TCGA), they were divided, in a 1:1 ratio, within training or test datasets. m6A‐related lncRNAs were then scrutinized across such dataset using Pearson correlation assessment before generating a m6A‐related lncRNAs prognosis‐related model using the training dataset. The latter was then validated with the test and the whole dataset. In addition, we compared the differences of TIM and the estimated IC50 of drug response between the high‐ and low‐risk groups.ResultsOverall survival (OS) resulted as linked with 11 m6A‐related lncRNAs, while within the developed prognosis‐related model, areas‐under‐curves were as follows: within training dataset, values at 3‐, 4‐, and 5‐years were 0.777, 0.819, and 0.805, accordingly, and for test one, they were 0.697, 0.682, and 0.706, respectively. Finally, the values for the whole dataset were 0.675 (3‐year), 0.682 (4‐years), and 0.679 (5‐years), accordingly. Moreover, CC cases categorized within low‐risk cohort demonstrated enhanced OS (p< .0001), lower metastasis (p= 2e‐06) and lower T stage (p= .0067), more instability for microsatellite status (p= .012), and downregulation forPD‐L1, PD‐1, CTLA‐4, LAG3, andHAVCR2(p< .05). In addition, risk scorings were significantly linked to the degree of infiltrative intensity for CD8 and CD4 (memory resting) T‐cells, T‐regulatory (Tregs), and Mast cells triggering (p< .05). Patients with low infiltrative propensity for CD4 T‐cells also had better OS (p= .016). Moreover, six representative drugs were found to be sensitive for treating CC patients.ConclusionA robust m6A‐related prognostic model with great performances was developed before exploring the TIM characteristics and its potential therapeutic drugs, which might improve the prognosis and therapeutic efficacy.