Abah Moses Owoicho, Ogenyi Deborah Oganya, Zhilenkova Angelina V, Essogmo Freddy Elad, Uchendu Ikenna Kingsley, Tchawe Yvan Sinclair Ngaha, Pascal Akaye Madu, Nikitina Natalia M, Oloche Onoja Solomon, Pavliv Maria, Rusanov Alexander S, Sanikovich Varvara D, Pirogova Yuliya N, Bagmet Leonid N, Moiseeva Aleksandra V, Sekacheva Marina I
World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov First Moscow State Medical University, Moscow 19991, Russia.
Department of Cancer Bioinformatics and Molecular Biology, Royal Society of Clinical and Academic Researchers (ROSCAR) International, Abuja 900104, Nigeria.
Int J Mol Sci. 2025 Jun 26;26(13):6161. doi: 10.3390/ijms26136161.
Currently, there is no standard treatment for renal cell carcinoma (RCC) that is free of side effects and resistance. Additionally, limited information exists on how curcumin affects the gene expression profiles of patients with translocation renal cell carcinoma (tRCC) and papillary renal cell carcinoma (pRCC). The pathways responsible for metastasis in tRCC are still not well understood, and there is no established treatment or reliable biomarker to predict outcomes for metastatic tRCC. Primary clinical data from patients were retrieved from the TCGA database and analyzed using cBioPortal, stitch, string, R and Python. Various analyses were performed, including differential gene expression, protein-protein interaction (PPI) network analysis, drug-targeted gene analysis, gene ontology (GO), enrichment analyses, and systematic searches to assess the impact of curcumin on the transcriptomic profiles of tRCC, pRCC, and clear cell renal cell carcinoma (ccRCC). No significant impact of sensitive genes on survival in KIRC and KIRP was found, though a trend suggested they may delay disease progression. The combination of curcumin with sunitinib showed promise in overcoming drug resistance in ccRCC by inducing ferroptosis, reducing iron, and increasing ADAMTS18 expression. This study, leveraging data from the TCGA database and other databases explored the impact of curcumin on transcriptomic profiles in tRCC, pRCC, and clear cell RCC (ccRCC). Gene analysis revealed immune and metabolic differences, with KIRC showing a stronger immune response. This study is the first to propose that future research into the miR-148/ADAMTS18 genes and the ferroptosis pathway in tRCC and pRCC could lead to the development of new therapies and the identification of novel therapeutic targets, potentially overcoming drug resistance and metastasis.
目前，尚无一种对肾细胞癌（RCC）无副作用且无耐药性的标准治疗方法。此外，关于姜黄素如何影响易位性肾细胞癌（tRCC）和乳头状肾细胞癌（pRCC）患者的基因表达谱的信息有限。tRCC中负责转移的途径仍未完全了解，并且尚无既定的治疗方法或可靠的生物标志物来预测转移性tRCC的预后。从TCGA数据库中检索患者的原始临床数据，并使用cBioPortal、stitch、string、R和Python进行分析。进行了各种分析，包括差异基因表达、蛋白质-蛋白质相互作用（PPI）网络分析、药物靶向基因分析、基因本体（GO）、富集分析以及系统搜索，以评估姜黄素对tRCC、pRCC和透明细胞肾细胞癌（ccRCC）转录组谱的影响。在KIRC和KIRP中未发现敏感基因对生存有显著影响，尽管有趋势表明它们可能会延缓疾病进展。姜黄素与舒尼替尼联合使用在克服ccRCC的耐药性方面显示出前景，通过诱导铁死亡、减少铁含量和增加ADAMTS18表达来实现。本研究利用TCGA数据库和其他数据库的数据，探讨了姜黄素对tRCC、pRCC和透明细胞RCC（ccRCC）转录组谱的影响。基因分析揭示了免疫和代谢差异，KIRC表现出更强的免疫反应。本研究首次提出，未来对tRCC和pRCC中的miR-148/ADAMTS18基因和铁死亡途径的研究可能会导致新疗法的开发和新治疗靶点的识别，有可能克服耐药性和转移。
