Saha Ayan, Sharmin Senzuti, Ahmed Tazin, Tabassum Sadia, Roy Ayan, Kar Pallab, Biswas Paromita, Ferdoush Jannatul
Department of Biological Sciences, Asian University for Women, Chittagong 4000, Bangladesh.
Department of Biochemistry and Microbiology, North South University, Dhaka 1229, Bangladesh; Science and Math Program, Asian University for Women, Chattogram 4000, Bangladesh.
J Genet Eng Biotechnol. 2025 Sep;23(3):100506. doi: 10.1016/j.jgeb.2025.100506. Epub 2025 Jun 4.
Kidney Renal Clear Cell Carcinoma (KIRC) is a leading cause of cancer death worldwide, but its early detection remains hindered by a lack of genetic markers. Our study aims to find prospective biomarkers that could serve as prognostic indicators and help in the identification of efficient drug candidates for KIRC treatment. Importantly, this study identifies the hub genes that play a crucial role in KIRC and their impact on male and female patients. The cBioPortal was used to identify frequently mutated genes across seven KIRC studies. Additionally, GSE168845 was employed to identify the differentially expressed genes. The analysis revealed that the titin (TTN) gene was mutated and upregulated in KIRC. Subsequently, differential genes of wild-type TTN versus mutant TTN were identified using TNMplot. The NetworkAnalyst tool was used to conduct KEGG analysis and PPI analysis on these genes. Furthermore, the Kaplan-Meier Plotter was utilized to perform overall survival analysis. Our findings indicated that the TTN gene leads to poorer prognosis in women than in men. We also discovered that the female-specific prolactin signaling pathway plays a significant role in the progression of KIRC. Moreover, our study suggested that the GDF15 gene, involved in the prolactin signaling pathway, has a worse prognosis for KIRC in women than in men. Additionally, mRNA expression analysis showed a negative correlation between GDF15 and MAPK14 in KIRC. Collectively, our research indicates that TTN, GDF15, and MAPK14 can serve as prognostic biomarkers in female KIRC patients, offering prospects for enhanced treatment and patient outcomes in these cancers.
肾透明细胞癌(KIRC)是全球癌症死亡的主要原因之一,但其早期检测仍因缺乏遗传标记而受阻。我们的研究旨在寻找可作为预后指标的前瞻性生物标志物,并有助于识别用于KIRC治疗的有效候选药物。重要的是,本研究确定了在KIRC中起关键作用的核心基因及其对男性和女性患者的影响。利用cBioPortal在七项KIRC研究中鉴定频繁突变的基因。此外,使用GSE168845鉴定差异表达基因。分析显示,肌联蛋白(TTN)基因在KIRC中发生突变并上调。随后,使用TNMplot鉴定野生型TTN与突变型TTN的差异基因。利用NetworkAnalyst工具对这些基因进行KEGG分析和蛋白质-蛋白质相互作用(PPI)分析。此外,使用Kaplan-Meier Plotter进行总生存分析。我们的研究结果表明,TTN基因导致女性预后比男性差。我们还发现,女性特异性催乳素信号通路在KIRC进展中起重要作用。此外,我们的研究表明,参与催乳素信号通路的GDF15基因在女性KIRC中的预后比男性差。此外,mRNA表达分析显示KIRC中GDF15与MAPK14之间呈负相关。总的来说,我们的研究表明,TTN、GDF15和MAPK14可作为女性KIRC患者的预后生物标志物,为改善这些癌症的治疗和患者预后提供了前景。