Prognostic Biomarkers for Survival in Nasopharyngeal Carcinoma: A Systematic Review of the Literature

Simple Summary Nasopharyngeal carcinoma (NPC) is an important Epstein-Barr virus (EBV)-associated malignancy. Currently, tumor-nodes-metastases (TNM) staging and tumor markers, such as EBV DNA, are widely used for prognostication; however, the identification of novel molecular biomarkers, especially related to genetics and epigenetics alterations of patients, can potentially provide additional prognostic repertoire to the existing clinical parameters and biomarkers; hence, provide a robust method for risk stratification and effective personalized therapy. This systematic review identifies seventeen such important molecular biomarkers, including germline single-nucleotide polymorphisms (SNP), methylation, microRNAs, mutation, and gene signatures in cancer and immune cells, with strong evidence and a low risk of bias, which can be used to predict NPC outcome. It also highlights the clinical need for a comprehensive evaluation of multiple types of biomarkers in a multicenter study. The biomarkers identified are involved in various signaling pathways, which could be exploited as therapeutic targets in a clinical setting. This systematic review aims to identify prognostic molecular biomarkers which demonstrate strong evidence and a low risk of bias in predicting the survival of nasopharyngeal carcinoma (NPC) patients. The literature was searched for on PubMed to identify original clinical studies and meta-analyses which reported associations between molecular biomarkers and survival, including >= 150 patients with a survival analysis, and the results were validated in at least one independent cohort, while meta-analyses must include >= 1000 patients with a survival analysis. Seventeen studies fulfilled these criteria-two studies on single nucleotide polymorphisms (SNPs), three studies on methylation biomarkers, two studies on microRNA biomarkers, one study on mutational signature, six studies on gene expression panels, and three meta-analyses on gene expressions. The comparison between the hazard ratios of high-risk and low-risk patients along with a multivariate analysis are used to indicate that these biomarkers have significant independent prognostic values for survival. The biomarkers also indicate a response to certain treatments and whether they could be used as therapeutic targets. This review highlights that patients' genetics, epigenetics, and signatures of cancer and immune cells in the tumor microenvironment (TME) play a vital role in determining their survival.