Investigation effect of Pembrolizumab antibody combined withNapabucasin compared with Pembrolizumab on the gene expression profiling in colorectal cancer based whole transcriptome RNA-Seq analysis

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide, being the second- and third-most frequently occurring cancer in women and men, respectively . Napabucasin has the potential to treat certain types of cancer by inhibiting the self-renewal and survival of cancer stem cells, as well as inducing apoptosis in both cancer stem cells and heterogeneous cancer cells. Pembrolizumab is a humanized monoclonal antibody (mAb) directed against the programmed cell death protein ۱ (PD-۱) that has been previously approved for the treatment of a variety of solid tumors. Material andMethod:DRP۰۰۸۲۴۹ dataset was downloaded from NCBI>SRA, the sra file was converted to two fastq paired files with sratoolkit.۲.۱۱.۳-ubuntu۶۴ software under Linux. Quality control of fastq files was performed with FASTQC software, and low quality reads were trimmed with Trimmomatic software and we mapped the trimmed file to hg۳۸ genome using Hisat۲ software and a sam file was obtained. In the next step, we converted the sam file to counts files using hg۳۸.ncbi.refseq.gtf and finally, DEGs were identified using the DESeq۲ package in R Studio software by threshold (FDR:۰.۰۵ and log۲foldchange>۱).Results:Based on the results, the e↵ect of Pembrolizumab antibody combined with Napabucasin in comparison with Pembrolizumab, cause of decreased the expression of PDE۱۰A, MALRD۱, FGFR۲, LOC۱۰۵۳۷۸۱۱۶ and GABRB۳ genes and increased the expression of LOC۱۰۵۳۷۱۳۰۸, ABO, ANKRD۱۸A, LINC۰۰۴۴۴ and E۴F۱ genes in tumor tissues of patients.Conclusion:Due to the important role of Pembrolizumab and Napabucasin antibodies in the process of apoptosis and treatment of a variety of solid tumors, identified genes can be used for prevention, diagnosis and as a therapeutic marker for patients with colorectal cancer.

کلیدواژه ها:

Colorectal cancer ، Pembrolizumab ، Napabucasin ، stem cells