Biological functions of RNA modification patterns that define tumor microenvironment and survival outcomes in testicular germ cell tumors.

Background: Accumulating evidence has indicated that aberrant RNA modifications are associated with malignant progression and the immune microenvironment in various tumors. However, the function of RNA modification regulators in testicular germ cell tumors (TGCTs) remains to be discovered. This study aimed to investigate the biological functions of RNA modification regulators in testicular germ cell tumors and identify their potential clinical predictive value.

Methods: Expression level of 75 RNA modification regulators was acquired to generate differential expression patterns. RNA modification regulatory genes were applied to construct a progression-free survival (PFS) risk model. Meanwhile, three RNA modification clusters were identified using consensus clustering. Subsequently, the infiltration characteristics of cells in the microenvironment as well as the antitumor drug candidates have been further analyzed. Finally, to further validate our results, we examined the expression and biological behavior of seven selected RNA modification regulators both in TGCT cell lines and clinical tissues.

Results: We collected the differentially expressed regulators of RNA modification. RNA modification risk signature was developed to stratify the prognosis of TGCT patients. Furthermore, we found significant differences in immune microenvironment between subgroups. Ultimately, seven selected RNA modification regulators were further verified.

Conclusions: We generated and validated a risk signature related to RNA modification which could accurately predict the relapse risk in TGCT patients. This risk signature was correlated with immune cells infiltration among tumor microenvironments. Furthermore, we screened antitumor drug candidates and evaluated the sensitivity and efficacy of class chemotherapeutic drugs, which could provide reference for clinical drug use.