Genetic Alterations in HSPA Family of Genes and their Putative Association with HNSCC
M. Laksita
Department of Microbiology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamilnadu, India.
J. Vijayashree Priyadharsini *
Clinical Genetics Lab, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamilnadu, India.
A. S. Smiline Girija
Clinical Genetics Lab, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamilnadu, India.
P. Sankar Ganesh
Clinical Genetics Lab, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamilnadu, India.
*Author to whom correspondence should be addressed.
Abstract
Introduction: Head and neck squamous cell carcinoma (HNSCC) is an aggressive life-threatening disease associated with high mortality rates. Several genes related to stress response have been studied extensively to reveal their possible association with HNSCC. Members of the HSPA (heat shock protein family A) family are exclusively expressed under stress conditions suggesting that these are specialised to function in the stress response.
Aim: The aim of the present study is to demonstrate the genetic alterations in the HSPA gene family and their putative association with HNSCC.
Materials and Methods: The source of the patient's data was procured from the cBioportal database. The TCGA Firehose Legacy comprised 528 head and neck squamous cell carcinoma cases. Oncoprint data analysis can be used to derive a putative association between the disease phenotype and genotype, to identify the variations and to identify any novel variations which can be associated with the disease phenotype. The gnomAD data analysis was used to compare between the observed variants documented in the present study with that of reported variants deposited in the gnomAD repository.
Results and Discussion: The HSPA1A&HSPA1B genes harboured high frequency of amplification and deep deletions. The expression of two genes HSPA8 and HSPA13 was found to be up-regulated in the primary tumor sample in comparison to normal tissues. In Kaplan Meier analysis, HSPA8 gene expression was compared with gender, here, high expression in females shows low survival rate. Similarly, HSPA13 gene expression was compared with race, here low expression in africanamerican population shows low survival rate.
Conclusion: The present study provides preliminary data on the involvement of the HSPA family of genes with HNSCC, which has to be validated using experimental evidence in other populations.
Keywords: Carcinoma, gene expression, heat shock proteins, novel mutations, protein stability