Kumar Vikrant, Tomar Anil Kumar, Thapliyal Ayushi, Yadav Savita
Department of Biophysics All India Institute of Medical Sciences, New Delhi 11029, India.
Biochem Res Int. 2024 Sep 13;2024:4288753. doi: 10.1155/2024/4288753. eCollection 2024.
Ovarian cancer's asymptomatic nature, high recurrence rate, and resistance to platinum-based chemotherapy highlight the need to find and characterize new diagnostic and therapeutic targets. While prior studies have linked aberrant expression of fibroblast growth factor 8 (FGF8) to various cancer types, its precise role has remained elusive. Recently, we observed that FGF8 silencing reduces the cancer-promoting properties of ovarian cancer cells, and thus, this study aimed to understand how FGF8 regulates the development of ovarian cancer. LC-MS/MS-based quantitative proteomics analysis identified 418 DEPs, and most of them were downregulated in FGF8-silenced ovarian cancer cells. Many of these DEPs are associated with cancer progression and unfavorable prognosis. To decipher the biological significance of DEPs, bioinformatics analyses encompassing gene ontology, pathway analysis, protein-protein interaction networks, and expression analysis of hub genes were carried out. Hub genes identified in the FGF8 protein network were upregulated in ovarian cancer compared to controls and were linked to poor prognosis. Subsequently, the expression of hub genes was correlated with patient survival and regulation of the tumor microenvironment. Conclusively, FGF8 and associated hub genes help in the progression of ovarian cancer, and their overexpression may lead to higher immune infiltration, poor prognosis, and poor survival.
卵巢癌的无症状特性、高复发率以及对铂类化疗的耐药性凸显了寻找和鉴定新的诊断及治疗靶点的必要性。虽然先前的研究已将成纤维细胞生长因子8(FGF8)的异常表达与多种癌症类型联系起来,但其确切作用仍不清楚。最近,我们观察到FGF8沉默会降低卵巢癌细胞的促癌特性,因此,本研究旨在了解FGF8如何调节卵巢癌的发展。基于液相色谱-串联质谱的定量蛋白质组学分析鉴定出418个差异表达蛋白(DEP),其中大多数在FGF8沉默的卵巢癌细胞中表达下调。这些DEP中的许多与癌症进展和不良预后相关。为了解析DEP的生物学意义,我们进行了包括基因本体论、通路分析、蛋白质-蛋白质相互作用网络以及枢纽基因表达分析在内的生物信息学分析。与对照组相比,在FGF8蛋白网络中鉴定出的枢纽基因在卵巢癌中上调,并且与不良预后相关。随后,枢纽基因的表达与患者生存率以及肿瘤微环境的调节相关。总之,FGF8及相关枢纽基因促进卵巢癌进展,它们的过表达可能导致更高的免疫浸润、不良预后和较差的生存率。