Zhang Yingai, Zhang Yuting, Zhou Shuai, Rehman Mujeeb Ur, Lin Fankai, Zhang Jianquan, Zhou Hailong
Central Laboratory, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, Hainan, 570208, China.
School of Life and Health Sciences, Hainan University, Haikou, Hainan, 570228, China.
BMC Cancer. 2025 Jan 31;25(1):185. doi: 10.1186/s12885-025-13575-5.
Hepatocellular carcinoma (HCC) has a poor prognosis, partly due to resistance to treatments like sorafenib. The 5-hydroxytryptamine receptor 1D (HTR1D) is involved in cancer progression through the PI3K/Akt pathway, but its role in HCC is not well understood. This study investigates HTR1D's expression, function, and potential as a prognostic marker in HCC.
First, the correlation between HTR1D and hepatocellular carcinoma was analyzed using the TCGA database, and the expression level of HTR1D in clinical samples was detected by qPCR. Then the siRNA was transfected into Huh-7 and Hep3B cells, and the cell proliferation ability, colony formation ability, migration and invasion ability were detected with or without sorafenib. And the expression of the PI3K/Akt pathway was detected by Western Blot. Finally, the potential of HTR1D as a predictive marker for patient prognosis was evaluated by immunohistochemistry.
Analysis of TCGA data showed that methylation of the HTR1D gene was associated with cancer status. Clinical samples confirmed significant differences in HTR1D expression between HCC and adjacent tissues, with higher expression correlating with poorer patient prognosis. Interference with HTR1D gene expression demonstrated its role in promoting HCC proliferation, migration, and drug resistance through the PI3K/Akt pathway. These findings were validated in a mouse model. Immunohistochemical analysis of clinicopathological samples suggested that HTR1D could be a valuable prognostic marker for HCC.
HTR1D is highly expressed in hepatocellular carcinoma tissues, and it can influence hepatocellular carcinoma development and resistance to sorafenib by regulating the PI3K/Akt signaling pathway. In addition, HTR1D has potential as a prognostic indicator.
肝细胞癌（HCC）预后较差，部分原因是对索拉非尼等治疗产生耐药性。5-羟色胺受体1D（HTR1D）通过PI3K/Akt途径参与癌症进展，但其在HCC中的作用尚不清楚。本研究调查HTR1D在HCC中的表达、功能及其作为预后标志物的潜力。
首先，使用TCGA数据库分析HTR1D与肝细胞癌之间的相关性，并通过qPCR检测临床样本中HTR1D的表达水平。然后将siRNA转染到Huh-7和Hep3B细胞中，在有或没有索拉非尼的情况下检测细胞增殖能力、集落形成能力、迁移和侵袭能力。通过蛋白质免疫印迹法检测PI3K/Akt途径的表达。最后，通过免疫组织化学评估HTR1D作为患者预后预测标志物的潜力。
TCGA数据分析表明，HTR1D基因的甲基化与癌症状态相关。临床样本证实HCC与癌旁组织中HTR1D表达存在显著差异，表达越高与患者预后越差相关。干扰HTR1D基因表达证明其通过PI3K/Akt途径促进HCC增殖、迁移和耐药。这些发现已在小鼠模型中得到验证。临床病理样本的免疫组织化学分析表明，HTR1D可能是HCC有价值的预后标志物。
HTR1D在肝细胞癌组织中高表达，它可通过调节PI3K/Akt信号通路影响肝细胞癌的发展和对索拉非尼的耐药性。此外，HTR1D有作为预后指标的潜力。
