Identification of microRNAs involved in the regulation of PDL-1 gene expression in gastric cancer tissue as diagnostic and therapeutic targets

Abstract

Introduction: Gastric cancer (GC) is one of the most significant causes of mortality in the world due to its rapid progress and late diagnosis of clinical factors. The high death rate in GC is mostly due to poor prognosis and the lack of effective treatments. Therefore, identifying novel and effective therapeutic and diagnostic targets for this malignancy is necessary. PD-L1 acts as a tumorigenic factor in cancer cells, especially GC, by binding to its receptors and activating proliferation and survival signaling pathways. In this regard, the identification of the molecular pathways involved in the regulation of the expression of this gene can lead to the identification of valuable molecular targets for the treatment and diagnosis of GC. Therefore, this study was conducted to identify microRNAs with therapeutic and diagnostic value involved in the regulation of PDL-1 gene expression in gastric cancer tissue. methods: First, by using past studies and relevant databases, microRNAs that target PD-L1 were identified as candidate microRNAs. Then, the expression of these genes in samples related to the TCGA-STAD dataset was evaluated to explore their possible role in GC. With the use of TCGA samples and ROC curve analysis, miR127 biomarker power was evaluated. Then, 25 gastric cancer tissue samples were obtained from the Iranian Tumor Bank along with healthy tissue samples adjacent to the patient. Next, the expression levels of PDL-1 and miR-127 genes were determined by qRT-PCR, and the relationship between these two genes was analyzed by Pearson correlation. Finally, to confirm the obtained results and determine the function of PDL-1 in gastric cancer progression, the data related to the expression of the PDL-1 gene in the TCGA database was also examined. Results: The results showed that the PDL-1 gene is significantly increased in gastric cancer tissues compared to healthy adjacent tissues, in line with TCGA results. Studies have shown that PDL-1 gene expression increases frequently in cancer progression and can be considered a general marker. On the other hand, our results showed a decrease in miR-127 expression in cancer samples compared to normal samples. Examining the relationship between PDL-1 gene expression and miR-127 also revealed a negative relationship between them, which confirmed this microRNA's ability to target PD-L1.