Investigating the Prediction of the Pathogenicity of p. Pro۱۴۶Arg Missense Mutation (rs۱۷۷۱۸۸۸۳) in the PD-L۱ Gene with a Bioinformatics Aproach

CD۲۷۴ gene is also known as PD-L۱. This gene is encoded on immune inhibitory receptorligand that is expressed by hematopoietic and non-hematopoietic cells, such as Tells and B cells, and isoverexpressed on the surface of various tumor cells. Interaction of this ligand with its receptor inhibitsT cell activation and cytokine production. During infection or inflammation of normal tissue, thisinteraction is important for preventing autoimmunity by maintaining homeostasis of the immuneresponse. In tumor microenvironments, this interaction provides an immune escape for tumor cellsthrough cytotoxic T-cell interaction. Expression of this gene in tumor cells is considered to be prognosticin many types of human malignancies, such as small-cell lung cancer (SCLC). SCLC is an extremelyaggressive subtype of cancer. The disease is characterized by rapid growth and early metastasis todistant organs. In this study, we have assessed a missense variation c.۴۳۷C>G (p. Pro۱۴۶Arg;rs۱۷۷۱۸۸۸۳) in the CD۲۷۴ gene. We evaluated this variation in prediction SNP servers and our resultsshow pathogenicity score in MAPP is ۸۶%, PhD-SNP is ۵۵%, PolyPhen-۱ is ۵۹%, PolyPhen-۲ is ۴۵%,SIFT is ۷۹%, SNAP is ۶۲% and PANTHER is ۵۶%. We also examined this variation in meta-SNP theresults are as follows PANTHER: ۰.۵۳۴, PhD-SNP: ۰.۴۱۲, SIFT: ۰.۱۰۰, SNAP: ۰.۵۷۵, and Meta-SNP:۰.۴۴۸. The hydrophobicity of protein measured by PEPTID-۲ changed from ۴۱.۰۳% to ۴۰.۶۹% withthis nucleotide change. Mutation taster also reported that this variation is disease-causing. According tothis in-silico study and prediction results, the rs۱۷۷۱۸۸۸۳ mutation might have pathogenic effects onthe CD۲۷۴ protein. This theory should be tested with experimental studies to confirm pathogeniceffects.

کلیدواژه ها:

PD-L۱ Gene ، CD۲۷۴ Gene ، Inhibitory Receptor Ligand ، Tumor Cell ، SCLC