Screening of differential gene expression patterns through survival analysis for diagnosis, prognosis and therapies of clear cell renal cell carcinoma

• Published in: PloS one 2024-09, Vol.19 (9), p.e0310843
• Main Authors: Ajadee, Alvira, Mahmud, Sabkat, Hossain, Md Bayazid, Ahmmed, Reaz, Ali, Md Ahad, Reza, Md Selim, Sarker, Saroje Kumar, Mollah, Md Nurul Haque
• Format: Article
• Language: English
• Subjects: Analysis; Biological activity; Biological effects; Biology and life sciences; Biomarkers, Tumor - genetics; Cancer; Carcinoma, Renal cell; Carcinoma, Renal Cell - diagnosis; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; CD4 antigen; CD8 antigen; Clear cell-type renal cell carcinoma; Datasets; Dendritic cells; Diagnosis; DNA methylation; DNA microarrays; Drug development; Drug resistance; Drugs; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Genes; Genetic aspects; Genomics; Humans; Imatinib; Immune system; Immunosuppressive agents; Irinotecan; Kidney Neoplasms - diagnosis; Kidney Neoplasms - drug therapy; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Kidneys; Leukocytes (neutrophilic); Literature reviews; Lymphocytes; Lymphocytes T; Macrophages; Medical prognosis; Medicine and Health Sciences; Metastases; Molecular docking; Molecular modelling; Network analysis; Post-transcription; Prognosis; Protein interaction; Protein Interaction Maps - genetics; Proteins; Receptors; Survival; Survival Analysis; Transcriptome
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0310843

Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of kidney cancer. Although there is increasing evidence linking ccRCC to genetic alterations, the exact molecular mechanism behind this relationship is not yet completely known to the researchers. Though drug therapies are the best choice after the metastasis, unfortunately, the majority of the patients progressively develop resistance against the therapeutic drugs after receiving it for almost 2 years. In this case, multi-targeted different variants of therapeutic drugs are essential for effective treatment against ccRCC. To understand molecular mechanisms of ccRCC development and progression, and explore multi-targeted different variants of therapeutic drugs, it is essential to identify ccRCC-causing key genes (KGs). In order to obtain ccRCC-causing KGs, at first, we detected 133 common differentially expressed genes (cDEGs) between ccRCC and control samples based on nine (9) microarray gene-expression datasets with NCBI accession IDs GSE16441, GSE53757, GSE66270, GSE66272, GSE16449, GSE76351, GSE66271, GSE71963, and GSE36895. Then, we filtered these cDEGs through survival analysis with the independent TCGA and GTEx database and obtained 54 scDEGs having significant prognostic power. Next, we used protein-protein interaction (PPI) network analysis with the reduced set of 54 scDEGs to identify ccRCC-causing top-ranked eight KGs (PLG, ENO2, ALDOB, UMOD, ALDH6A1, SLC12A3, SLC12A1, SERPINA5). The pan-cancer analysis with KGs based on TCGA database showed the significant association with different subtypes of kidney cancers including ccRCC. The gene regulatory network (GRN) analysis revealed some crucial transcriptional and post-transcriptional regulators of KGs. The scDEGs-set enrichment analysis significantly identified some crucial ccRCC-causing molecular functions, biological processes, cellular components, and pathways that are linked to the KGs. The results of DNA methylation study indicated the hypomethylation and hyper-methylation of KGs, which may lead the development of ccRCC. The immune infiltrating cell types (CD8+ T and CD4+ T cell, B cell, neutrophil, dendritic cell and macrophage) analysis with KGs indicated their significant association in ccRCC, where KGs are positively correlated with CD4+ T cells, but negatively correlated with the majority of other immune cells, which is supported by the literature review also. Then we detected 10 repurposable drug molecules (Irinotecan,