Sharma Revati, Balta Showan, Raza Ali, Escalona Ruth M, Kannourakis George, Prithviraj Prashanth, Ahmed Nuzhat
Fiona Elsey Cancer Research Institute, Ballarat, VIC 3353, Australia.
Health Innovation and Transformation Centre, Mt Helen Campus, Federation University Australia, Ballarat, VIC 3350, Australia.
Cancers (Basel). 2023 May 1;15(9):2586. doi: 10.3390/cancers15092586.
The process of epithelial-mesenchymal transition (EMT) involves the phenotypic transformation of cells from epithelial to mesenchymal status. The cells exhibiting EMT contain features of cancer stem cells (CSC), and the dual processes are responsible for progressive cancers. Activation of hypoxia-inducible factors (HIF) is fundamental to the pathogenesis of clear cell renal cell carcinoma (ccRCC), and their role in promoting EMT and CSCs is crucial for ccRCC tumour cell survival, disease progression, and metastatic spread. In this study, we explored the status of HIF genes and their downstream targets, EMT and CSC markers, by immunohistochemistry on in-house accrued ccRCC biopsies and adjacent non-tumorous tissues from patients undergoing partial or radical nephrectomy. In combination, we comprehensively analysed the expression of HIF genes and its downstream EMT and CSC-associated targets relevant to ccRCC by using publicly available datasets, the cancer genome atlas (TCGA) and the clinical proteome tumour analysis consortium (CPTAC). The aim was to search for novel biological prognostic markers that can stratify high-risk patients likely to experience metastatic disease. Using the above two approaches, we report the development of novel gene signatures that may help to identify patients at a high risk of developing metastatic and progressive disease.
上皮-间质转化（EMT）过程涉及细胞从上皮状态向间质状态的表型转变。表现出EMT的细胞具有癌症干细胞（CSC）的特征，这两个过程共同导致癌症进展。缺氧诱导因子（HIF）的激活是透明细胞肾细胞癌（ccRCC）发病机制的基础，其在促进EMT和CSC方面的作用对于ccRCC肿瘤细胞存活、疾病进展和转移扩散至关重要。在本研究中，我们通过免疫组织化学方法，对接受部分或根治性肾切除术患者的ccRCC活检组织及相邻非肿瘤组织进行分析，以探究HIF基因及其下游靶点、EMT和CSC标志物的状态。同时，我们利用公开可用的数据集癌症基因组图谱（TCGA）和临床蛋白质组肿瘤分析联盟（CPTAC），综合分析与ccRCC相关的HIF基因及其下游EMT和CSC相关靶点的表达。目的是寻找能够对可能发生转移性疾病的高危患者进行分层的新型生物学预后标志物。通过上述两种方法，我们报告了可能有助于识别发生转移性和进展性疾病高危患者的新型基因特征的开发情况。
