Biochemistry and Molecular Biology Lab, Institute of Clinical Physiology - National Research Council CNR, Via Giuseppe Moruzzi 1, 56124, Pisa, Italy.
Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy.
Clin Exp Metastasis. 2022 Aug;39(4):589-602. doi: 10.1007/s10585-022-10164-9. Epub 2022 Apr 16.
Hepatocellular carcinoma (HCC) is one of the main cancer-related causes of death worldwide. The study aimed to perform a data mining analysis of the expression and regulatory role of key genes in HCC to reveal novel potential biomarkers of diagnosis prognosis, or progression since their availability is still almost lacking. Starting from data of our cohort of patients (HCV-positive HCC pts undergoing liver transplantation (LR, n = 10) and donors (LD, n = 14), deeply analyzed previously, in which apelin, osteopontin, osteoprotegerin, NOTCH-1, CASP-3, Bcl-2, BAX, PTX3, and NPTX2 were analyzed, we applied statistical analysis and in-silico tools (Gene Expression Profiling Interactive Analysis, HCCDB database and GeneMania, UALCAN) to screen and identify the key genes. Firstly, we performed a stepwise regression analysis using our mRNA-datasets which revealed that higher expression levels of apelin and osteopontin were positively associated with the HCC and identified that the most consistently differentially expressed gene across multiple HCC expression datasets was only OPN. This comprehensive strategy of data mining evidenced that OPN might have a potential function as an important tumor marker-driven oncogenesis being associated with poor prognosis of HCC patients.
肝细胞癌 (HCC) 是全球主要的癌症相关死亡原因之一。本研究旨在对 HCC 中关键基因的表达和调控作用进行数据挖掘分析,以揭示新的潜在诊断预后或进展的生物标志物,因为它们的可用性几乎仍然缺乏。从我们之前深度分析的患者队列(HCV 阳性 HCC 患者接受肝移植 (LR,n=10) 和供体 (LD,n=14))的数据开始,其中分析了 Apelin、Osteopontin、Osteoprotegerin、NOTCH-1、CASP-3、Bcl-2、BAX、PTX3 和 NPTX2,我们应用统计分析和计算工具(Gene Expression Profiling Interactive Analysis、HCCDB 数据库和 GeneMania、UALCAN)来筛选和识别关键基因。首先,我们使用我们的 mRNA 数据集进行逐步回归分析,结果表明 Apelin 和 Osteopontin 的高表达水平与 HCC 呈正相关,并确定了在多个 HCC 表达数据集上表达最一致的差异基因仅为 OPN。这种数据挖掘的综合策略表明,OPN 可能具有作为重要肿瘤标志物驱动肿瘤发生的潜在功能,与 HCC 患者的不良预后相关。