Deciphering the Genetic Alterations in SPARC Gene Family and Its Association with HNSCC

Abstract

The aim of this study is to identify the genetic alteration in SPARC gene family and its association with head and neck squamous cell carcinoma (HNSCC). Head and neck cancer is a set of cancerous lesions arising from the squamous cell of the mucous membrane of the oral cavity, nose throat, larynx and pharynx. SPARC gene encodes for cysteine rich acid matrix metalloprotein, osteonectin whose expression in metastatic OSCC (Oral squamous cell carcinoma) was found to be higher. This expression pattern also correlated with the worst pattern of invasion and differentiation of OSCC tumors. In line with the above facts, the present study was carried out to ascertain the gene alterations and their consequences. Also the putative association of gene alterations with HNSCC was analyzed using computational tools. The Cancer Gene Atlas (TCGA, Firehose Legacy) dataset hosted by the cBioportal server was used in the present study. The non-synonymous variants identified were further assessed for protein stability and pathogenicity employing IMutant and PROVEAN tools. Gene amplification was observed in the FSTL1 gene, which was also shown to present with the highest frequency of gene alterations (5%) among eight genes. Furthermore, the expression of the FSTL1 gene was found to differ significantly among different grades of HNSCC. In conclusion, the study throws light on the possible association of the FSTL1 gene of the SPARC family with HNSCC.