Exploration of a Novel Prognostic Risk Signature and Its Effect on the Immune Response in Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic carcinoma with different molecular characteristics and clinical outcomes. In this work, we aimed to establish a novel gene signature that could predict the prognosis of NPC patients. A total of 13 significant genes between the recurrence/metastasis (RM) group and the no recurrence/metastasis (no-RM) group were identified by machine learning from RNA-Seq data including 60 NPC tumor biopsies. Based on these genes, a 4-mRNA signature (considering U2AF1L5, TMEM265, GLB1L and MLF1) was identified. Receiver operating characteristic (ROC) and Kaplan-Meier (K-M) analyses indicated that this signature had good prognostic value for NPC. The overall survival (OS) and progression-free survival (PFS) of the patients in the high-risk group were significantly shorter than those of the patients in the low-risk group (p = 0.00126 and p = 0.000059, respectively). The area under the ROC curve (AUC) values of the 4-mRNA signature were higher than those of T stage and N stage for OS (0.893 vs 0.619 and 0.582, respectively) and PFS (0.86 vs 0.538 and 0.622, respectively). Furthermore, the 4-mRNA signature was closely associated with cell proliferation and the immune response. The expression of GLB1L and TMEM265 was associated with the level of tumor-infiltrating immune cells (r > 0.4, p < 0.05). We have validated the model through measuring the expression levels of the 4-mRNA signature by qRT-PCR, in an independent cohort of NPC patients. Here, we report a novel gene signature that can serve as a new tool for predicting the prognosis of NPC patients.