Decoding the Genetic Alterations in PRAME Gene Family and Its Association with Head and Neck Squamous Cell Carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the most common form of cancer with an incidence rate greater in male than in female. Advancements in molecular diagnostics have identified several pathways which can have a direct or indirect role in the development and progression of HNSCC. The PRAME (PReferentially Antigen expressed in MElanoma) gene family is yet another group of genes which has been recently implicated in HNSCC. The present study aims to identify the genetic alterations, the pattern of gene expression and the consequence of mutations in the PRAME family of genes in HNSCC patients. Several databases such as cBioportal, gnomAD, IMutant, PROVEAN were used to assess genetic alterations. The alterations included deep deletions, amplification, inframe, missense, truncating mutations. The gene showing the highest frequency of alteration (PRAME - 3%) was further assessed for its gene expression profile using the UALCAN database. The expression profile relative to normal samples was found to be significantly higher in HNSCC patients (p = 1.11 x 10-16). Further, the survival curve based on high and low/medium expression of the PRAME gene was assessed by Kaplan-Meier method. The analysis revealed a significant difference in the survival rate of patients with high and low/medicum level expression (0.0095). In addition, the high level expression was found to be associated with poor survival rate in HNSCC patients compared to those exhibiting low and medium level expression. In conclusion the study provides insights into the putative association of genes of the PRAME family with HNSCC. The preliminary results have to be further validated using experimental procedures.