Caliskan Aysegul, Gulfidan Gizem, Sinha Raghu, Arga Kazim Yalcin
Department of Bioengineering, Marmara University, Istanbul 34722, Turkey.
Faculty of Pharmacy, Istinye University, Istanbul 34010, Turkey.
J Pers Med. 2021 Feb 23;11(2):158. doi: 10.3390/jpm11020158.
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-protein 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.
尽管已经对癌症患者的单基因疗法进行了许多研究，但实际情况是肿瘤源自不同的协同蛋白质组。揭示与肿瘤形成相关的蛋白质相互作用组中的扰动可能有助于开发有效的诊断、治疗策略和预后方法。在本研究中，考虑到从癌症基因组图谱（TCGA）检索到的三种肾细胞癌（RCC）亚型（ccRCC、pRCC和chRCC）的临床和转录组数据以及人类蛋白质相互作用组，在每种RCC亚型中鉴定了差异蛋白质-蛋白质相互作用。该方法能够识别差异相互作用蛋白（DIP），这些蛋白表明它们在肿瘤形成过程中的相互作用模式发生了显著变化。此外，通过考虑特定于相关亚型的DIP簇，生成了诊断和预后性能。此外，将间充质上皮转化（MET）受体酪氨酸激酶（PDB ID：3DKF）视为pRCC特有的潜在药物靶点，通过对ZINC分子进行虚拟筛选鉴定了21种先导化合物。在本研究中，我们在早期诊断、预后和有效治疗策略方面提出了显著的发现，值得进一步的实验和临床研究。
