AUTHOR=Qadir Jasiya , Majid Sabhiya , Khan Mosin Saleem , Rashid Fouzia , Wani Mumtaz Din , Bhat Showkat Ahmad 

TITLE=Implication of ARID1A Undercurrents and PDL1, TP53 Overexpression in Advanced Gastric Cancer

JOURNAL=Pathology and Oncology Research

VOLUME=27

YEAR=2021

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2021.1609826

DOI=10.3389/pore.2021.1609826

ISSN=1532-2807

ABSTRACT=<p>AT-rich interactive domain-containing protein 1A (ARID1A), TP53 and programmed cell death-ligand 1 (PDL1) are involved in several protein interactions that regulate the expression of various cancer-related genes involved in the progression of the cell cycle, cell proliferation, DNA repair, and apoptosis. In addition, gene expression analysis identified some common downstream targets of ARID1A and TP53. It has been established that tumors formed by <italic>ARID1A</italic>-deficient cancer cells exhibited elevated <italic>PDL1</italic> expression. However, the aberrations in these molecules have not been studied in this population especially in Gastric Cancer (GC). In this backdrop we aimed to investigate the role of the <italic>ARID1A</italic> mutation and expression of <italic>ARID1A</italic>, <italic>TP53</italic> and <italic>PDL1</italic> genes in the etiopathogenesis of Gastric Cancer (GC) in the ethnic Kashmiri population (North India). The study included 103 histologically confirmed GC cases. The mutations, if any, in exon-9 of <italic>ARID1A</italic> gene was analysed by Polymerase Chain Reaction (PCR) followed by Sanger sequencing. The mRNA expression of the <italic>ARID1A</italic>, <italic>TP53</italic> and <italic>PDL1</italic> genes was analysed by Quantitative real time-PCR (qRT-PCR). We identified a nonsense mutation (c.3219; C &gt; T) in exon-9 among two GC patients (∼2.0%), which introduces a premature stop codon at protein position 1073. The mRNA expression of the <italic>ARID1A, TP53</italic> and <italic>PDL1</italic> gene was significantly reduced in 25.3% and elevated in 47.6 and 39.8% of GC cases respectively with a mean fold change of 0.63, 2.93 and 2.43. The data revealed that reduced mRNA expression of <italic>ARID1A</italic> and elevated mRNA expression of <italic>TP53</italic> and <italic>PDL1</italic> was significantly associated with the high-grade and advanced stage of cancer. Our study proposes that <italic>ARAD1A</italic> under-expression and overexpression of <italic>TP53</italic> and <italic>PDL1</italic> might be crucial for tumor progression with <italic>TP53</italic> and <italic>PDL1</italic> acting synergistically.</p>