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Advances in tumor diagnosis, innovative immune therapeutics, and checkpoint inhibitors-based treatment options improved the survival rate of patients with RCC accompanied by different risk factors. RCC patients with diabetes, hepatitis C virus (HCV), or obesity (OB) may have a comorbidity, and finding the risk factor for better clinical treatment is an urgent issue. Therefore, the study focused on network-based gene expression analysis approaches to learning the impact of RCC on other comorbidities associated with the disease. The study found critical genetic factors and signal transduction pathways that share pathophysiology and commonly use dysregulated genes of the illness. Initially, the study identified 385 up-regulated genes and 338 down-regulated genes involved with RCC. OB, chronic kidney disease (CKD), type 2 diabetes (T2D), and HCV significantly shared 28, 14, 5, and 3 genes, respectively. RCC shared one down-regulated gene versican (VCAN) with OB and HCV and one down-regulated gene oxidase homolog 2 (LOXL2) with OB and CKD. Interestingly, most of the shared pathways were linked with metabolism. The study also identified six prospective biomarkers, signaling pathways, and numerous critical regulatory and associated drug candidates for the disease. We believe that the discovery will help explain these diseases\u2019 complicated interplay and aid in developing novel therapeutic targets and drug candidates.<\/jats:p>","DOI":"10.1042\/bsr20221108","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T12:38:02Z","timestamp":1667219882000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["System biology approaches identified novel biomarkers and their signaling pathways involved in renal cell carcinoma with different human diseases"],"prefix":"10.1042","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8258-3291","authenticated-orcid":false,"given":"Md.\u00a0Saddam","family":"Hossen","sequence":"first","affiliation":[{"name":"1College of Life Sciences and Medicine, Zhejiang Sci-Tech University, 310018 Hangzhou, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdus","family":"Samad","sequence":"additional","affiliation":[{"name":"2Laboratory of Computational Biology, Biological Solution Centre (BioSol Centre), Jashore 7408, Bangladesh"},{"name":"3Department of Genetic Engineering and Biotechnology, Faculty of Biological Science, Jashore University of Science and Technology, Jashore 7408, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7313-4729","authenticated-orcid":false,"given":"Foysal","family":"Ahammad","sequence":"additional","affiliation":[{"name":"2Laboratory of Computational Biology, Biological Solution Centre (BioSol Centre), Jashore 7408, Bangladesh"},{"name":"4Department of Biological Sciences, Faculty of Science, King Abdul-Aziz University, Jeddah 21589, Saudi Arabia"},{"name":"5Division of Biological and Biomedical Sciences (BBS), College of Health & Life Sciences (CHLS), Hamad Bin Khalifa University (HBKU), Doha 34110, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2861-0674","authenticated-orcid":false,"given":"Gabriel\u00a0B.K.","family":"Sasa","sequence":"additional","affiliation":[{"name":"1College of Life Sciences and Medicine, Zhejiang Sci-Tech University, 310018 Hangzhou, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenggang","family":"Jiang","sequence":"additional","affiliation":[{"name":"6Department of Science Research and Information Management, Zhejiang Provincial Centers for Disease Control and Prevention, Hangzhou 310051, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianfeng","family":"Ding","sequence":"additional","affiliation":[{"name":"1College of Life Sciences and Medicine, Zhejiang Sci-Tech University, 310018 Hangzhou, People\u2019s Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2022,11,21]]},"reference":[{"key":"2022112112361569200_B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nrdp.2017.9","article-title":"Renal cell carcinoma","volume":"3","author":"Hsieh","year":"2017","journal-title":"Nat. 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