{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T03:30:24Z","timestamp":1772681424055,"version":"3.50.1"},"reference-count":31,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T00:00:00Z","timestamp":1614038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Although many studies have been conducted on single gene therapies in cancer patients, the reality is that tumor arises from different coordinating protein groups. Unveiling perturbations in protein interactome related to the tumor formation may contribute to the development of effective diagnosis, treatment strategies, and prognosis. In this study, considering the clinical and transcriptome data of three Renal Cell Carcinoma (RCC) subtypes (ccRCC, pRCC, and chRCC) retrieved from The Cancer Genome Atlas (TCGA) and the human protein interactome, the differential protein\u2013protein interactions were identified in each RCC subtype. The approach enabled the identification of differentially interacting proteins (DIPs) indicating prominent changes in their interaction patterns during tumor formation. Further, diagnostic and prognostic performances were generated by taking into account DIP clusters which are specific to the relevant subtypes. Furthermore, considering the mesenchymal epithelial transition (MET) receptor tyrosine kinase (PDB ID: 3DKF) as a potential drug target specific to pRCC, twenty-one lead compounds were identified through virtual screening of ZINC molecules. In this study, we presented remarkable findings in terms of early diagnosis, prognosis, and effective treatment strategies, that deserve further experimental and clinical efforts.<\/jats:p>","DOI":"10.3390\/jpm11020158","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T12:40:16Z","timestamp":1614084016000},"page":"158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Differential Interactome Proposes Subtype-Specific Biomarkers and Potential Therapeutics in Renal Cell Carcinomas"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1887-9167","authenticated-orcid":false,"given":"Aysegul","family":"Caliskan","sequence":"first","affiliation":[{"name":"Department of Bioengineering, Marmara University, Istanbul 34722, Turkey"},{"name":"Faculty of Pharmacy, Istinye University, Istanbul 34010, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4150-0012","authenticated-orcid":false,"given":"Gizem","family":"Gulfidan","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Marmara University, Istanbul 34722, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9083-8533","authenticated-orcid":false,"given":"Raghu","family":"Sinha","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6036-1348","authenticated-orcid":false,"given":"Kazim Yalcin","family":"Arga","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Marmara University, Istanbul 34722, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"507","DOI":"10.3322\/caac.21411","article-title":"Treatment of renal cell carcinoma: Current status and future directions","volume":"67","author":"Barata","year":"2017","journal-title":"CA Cancer J. 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