Karaoglu Diren Arda, Uner Meral, Simsek Cem, Gure Ali Osmay, Demirkol-Canli Secil
Faculty of Medicine, Hacettepe University, 06100 Ankara, Turkey.
Department of Pathology, Hacettepe University Faculty of Medicine, Sıhhiye, 06100 Ankara, Turkey.
Biology (Basel). 2023 Jan 26;12(2):188. doi: 10.3390/biology12020188.
Hepatocellular cancer (HCC) is a leading cause of cancer-related mortality worldwide, and chronic hepatitis B virus infection (CHB) has been a major risk factor for HCC development. The pathogenesis of HBV-related HCC has been a major focus revealing the interplay of a multitude of intracellular signaling pathways, yet the precise mechanisms and their implementations to clinical practice remain to be elucidated. This study utilizes publicly available transcriptomic data from the livers of CHB patients in order to identify a population with a higher risk of malignant transformation. We report the identification of a novel list of genes (PCM1) which can generate clear transcriptomic sub-groups among HBV-infected livers. PCM1 includes genes related to cell cycle activity and liver cancer development. In addition, markers of inflammation, M1 macrophages and gamma delta T cell infiltration are present within the signature. Genes within PCM1 are also able to differentiate HCC from normal liver, and some genes within the signature are associated with poor prognosis of HCC at the mRNA level. The analysis of the immunohistochemical stainings validated that proteins coded by a group of PCM1 genes were overexpressed in liver cancer, while minimal or no expression was detected in normal liver. Altogether, our findings suggest that PCM1 can be developed into a clinically applicable method to identify CHB patients with a higher risk of HCC development.
肝细胞癌(HCC)是全球癌症相关死亡的主要原因之一,慢性乙型肝炎病毒感染(CHB)一直是HCC发生的主要危险因素。HBV相关HCC的发病机制一直是揭示众多细胞内信号通路相互作用的主要研究重点,但确切机制及其在临床实践中的应用仍有待阐明。本研究利用CHB患者肝脏的公开转录组数据,以识别具有更高恶性转化风险的人群。我们报告了一个新的基因列表(PCM1)的鉴定,该基因列表可以在HBV感染的肝脏中产生明确的转录组亚组。PCM1包括与细胞周期活性和肝癌发生相关的基因。此外,炎症标志物、M1巨噬细胞和γδT细胞浸润也存在于该特征中。PCM1中的基因还能够区分HCC与正常肝脏,并且该特征中的一些基因在mRNA水平上与HCC的不良预后相关。免疫组织化学染色分析证实,一组PCM1基因编码的蛋白质在肝癌中过度表达,而在正常肝脏中检测到极少或无表达。总之,我们的研究结果表明,PCM1可以发展成为一种临床适用的方法,用于识别具有更高HCC发生风险的CHB患者。