BackgroundRecently, immune response modulation at epigenetic level is illustrated in studies, but it is still unclear about the possible function of RNA 5-methylcytosine (m5C) modification in the cell infiltration within tumor microenvironment (TME).MethodsIn this study, the m5C modification patterns from altogether 493 papillary thyroid carcinoma (PTC) samples were assessed completely according to 9 m5C regulators. Afterwards, the modification patterns were correlated with the cell infiltration features in TME. The m5C modification patterns in tumor samples were quantified through the principal component analysis (PCA) algorithms to establish the m5C-score. Moreover, this study mined the signature genes related to the m5C-score, constructed the PTC diagnostic model by the support vector machine (SVM) method, and verified its accuracy based on samples in TCGA and GEO databases. The effects of 5 potential drugs based on the PTC m5C-score model in PTC cells were investigated through in vitro and in vivo assays (i.e., cell counting kit 8 and xenograft model). ResultsA total of 3 different m5C modification patterns were identified, and high differentiation degree was observed in the cell infiltration features within TME under the above 3 identified patterns. It was revealed that, evaluating m5C modification patterns in single tumor samples helped to estimate the stromal activity in TME, expression of immune checkpoint genes, and prognosis for patients. Typically, a low m5C-score, which was reflected in the activated immunity, predicted the relatively favorable prognostic outcome. Few effective immune infiltration was seen in high m5C-score subtype, indicating the dismal patient survival. Finally, this study constructed a diagnostic model using the 10 signature genes highly related to the m5C-score, discovered that the model exhibited high diagnostic accuracy for PTC, and screened out 5 potential drugs for PTC based on this m5C-score model. ConclusionsAccording to findings in the present study, m5C modification exerts an important part in forming the TME complexity and diversity. It is valuable to evaluate the m5C modification patterns in single tumors, so as to enhance our understanding towards the infiltration characterization in TME and to better guide clinical diagnosis as well as immunotherapies.