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Deciphering key genes involved in cisplatin resistance in kidney renal clear cell carcinoma through a combined in silico and in vitro approach

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肿瘤学研究(英文) 2023年第6期31卷 899-916页

作者： MUNEEBA MALIK MAMOONA MAQBOOL TOOBA NISAR tazeem akhter JAVED AHMED UJAN ALANOOD SALGARNI FAKHRIA AAL JOUFI SULTAN SHAFI KALANAZI MOHAMMAD HADI ALMOTARED MOUNIR MSALEM BEKHIT MUHAMMAD JAMIL Services Hospital LahorePakistan Sabzazar Medical Center LahorePakistan BHU Pourmiana AttockPakistan Public Health Department University of Health SciencesLahorePakistan Department of Zoology Shah Abdul Latif UniversityKhairpurPakistan Department of Animal Sciences University of FloridaGainesvilleUSA Pharmacology and Toxicology Department College of Pharmacy Umm Al-Qura UniversityMakkahSaudi Arabia Department of Pharmacology College of PharmacyJouf UniversityAljoufSaudi Arabia Regional Laboratory and Blood Bank(Total Laboratory Automation) RiyadhSaudi Arabia Health Affairs in Najran New Najran General HospitalNajranSaudi Arabia Department of Pharmaceutics College of PharmacyKing Saud UniversityRiyadhSaudi Arabia PARC Arid Zone Research Center Dera Ismail KhanPakistan

The low survival rate of Kidney renal clear cell carcinoma(KIRC)patients is largely attributed to cisplatin *** than focusing solely on individual proteins,exploring protein-protein interactions could offer greater insight into drug *** this end,a series of in silico and in vitro experiments were conducted to identify hub genes in the intricate network of cisplatin resistance-related genes in KIRC *** genes involved in cisplatin resistance across KIRC were retrieved from the National Center for Biotechnology Information(NCBI)database using search terms as“Kidney renal clear cell carcinoma”and“Cisplatin resistance”.The genes retrieved were analyzed for hub gene identification using the STRING database and Cytoscape *** and promoter methylation profiling of the hub genes was done using UALCAN,GEPIA,OncoDB,and HPA ***,survival,functional enrichment,immune cell infiltration,and drug prediction analyses of the hub genes were performed using the cBioPortal,GEPIA,GSEA,TIMER,and DrugBank ***,expression and methylation levels of the hub genes were validated on two cisplatin-resistant RCC cell lines(786-O and A-498)and a normal renal tubular epithelial cell line(HK-2)using two high throughput techniques,including targeted bisulfite sequencing(bisulfite-seq)and RT-qPCR.A total of 124 genes were identified as being associated with cisplatin resistance in *** of these genes,MCL1,IGF1R,CCND1,and PTEN were identified as hub genes and were found to have significant(p<0.05)variations in their mRNA and protein expressions and effects on the overall survival(OS)of the KIRC ***,an aberrant promoter methylation pattern was found to be associated with the dysregulation of the hub *** addition to this,hub genes were also linked with different cisplatin resistance-causing ***,hub genes can be targeted with Alvocidib,Estradiol,Tretinoin,Capsaicin,Dronabinol,Metribolone,Calcitriol

关键词： KIRC Cisplatin resistance Chemotherapy Overall survival

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