南方医科大学学报

南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (10): 2135-2145.doi: 10.12122/j.issn.1673-4254.2025.10.10

• • 上一篇    

高表达甲状旁腺激素样激素促进肝细胞癌的进展并与患者预后不良相关

缪祥卓1(), 朱鹏宇1(), 区活辉1,4, 朱庆1, 于林源1, 郭柏棠1, 廖渭5, 黄毓2, 相乐阳3(), 杨定华1()   

  1. 1.南方医科大学南方医院，肝胆外科，广东 广州 510515
    2.南方医科大学南方医院，检验科，广东 广州 510515
    3.暨南大学附属第一医院肝胆外科，广东 广州 510630
    4.南方医科大学顺德医院肝胆外科，广东 顺德 528399
    5.佛山市第一人民医院肝胆外科，广东 佛山 528000
  • 收稿日期:2025-03-25 出版日期:2025-10-20 发布日期:2025-10-24
  • 通讯作者: 相乐阳,杨定华 E-mail:u201712361@163.com;zpy0511@126.com;xly1991@jnu.edu.cn;yangdinghua@smu.edu.cn
  • 作者简介:缪祥卓，在读硕士研究生，E-mail: u201712361@163.com
    朱鹏宇，在读硕士研究生，E-mail: zpy0511@126.com
    第一联系人：共同第一作者
  • 基金资助:
    国家自然科学基金(82372851)

Overexpression of parathyroid hormone-like hormone facilitates hepatocellular carcinoma progression and correlates with adverse outcomes

Xiangzhuo MIAO1(), Pengyu ZHU1(), Huohui OU1,4, Qing ZHU1, Linyuan YU1, Baitang GUO1, Wei LIAO5, Yu HUANG2, Leyang XIANG3(), Dinghua YANG1()   

  1. 1.Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
    2.Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
    3.Department of Hepatobiliary Surgery, First Affiliated Hospital of Jinan University, Guangzhou 510630, China
    4.Department of Hepatobiliary Surgery, Shunde Hospital, Southern Medical University, Shunde 528399, China
    5.Department of Hepatobiliary Surgery, Foshan First People's Hospital, Foshan 528000, China
  • Received:2025-03-25 Online:2025-10-20 Published:2025-10-24
  • Contact: Leyang XIANG, Dinghua YANG E-mail:u201712361@163.com;zpy0511@126.com;xly1991@jnu.edu.cn;yangdinghua@smu.edu.cn
  • Supported by:
    National Natural Science Foundation of China(82372851)

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摘要：

目的 探究甲状旁腺激素样激素（PTHLH）在肝细胞癌（HCC）中的表达水平，分析其与患者临床预后的关系，并探究其对HCC细胞生物学行为的影响及可能的作用通路。 方法 基于癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的数据，结合本院收治的70例HCC患者的临床样本，分析PTHLH在HCC组织和癌旁组织中的表达水平差异及其与患者临床预后的关系。体外培养HCC细胞，通过敲低和过表达PTHLH，采用CCK-8实验、克隆形成实验、Transwell迁移和侵袭实验评估PTHLH对HCC细胞增殖、迁移和侵袭能力的影响；Western blotting分析PTHLH可能激活的信号通路。 结果 TCGA和GEO数据库分析显示，PTHLH mRNA在HCC组织中显著高表达，且与患者不良预后相关（P<0.05），PTHLH mRNA高表达可能是Huh7和Hep3B患者的独立预后危险因素（P<0.05）。通过临床样本对数据库结果进行验证，HCC组织中PTHLH mRNA表达水平高于癌旁组织（P<0.001），免疫组织化学染色分析也显示PTHLH蛋白在HCC组织中的表达水平显著升高（P<0.01）。单因素和多因素Cox回归分析表明，PTHLH mRNA高表达可能是影响HCC患者术后无瘤生存时间的独立危险因素（P<0.05），且基于PTHLH mRNA表达水平构建的预后预测模型提高了HCC患者术后复发风险的预测准确性。进一步的体外细胞实验结果显示，PTHLH可促进Huh7和Hep3B细胞的增殖（P<0.01）和克隆形成（P<0.01）；增强Huh7和Hep3B细胞的迁移和侵袭能力（P<0.01）；Western blotting分析显示，PTHLH可能通过激活ERK/JNK信号通路发挥其促癌作用。 结论 高表达PTHLH促进肝细胞癌的进展与患者预后不良相关，其促癌效应可能是通过激活ERK/JNK信号通路实现的。

关键词: 肝细胞癌, 甲状旁腺激素样激素, 临床预后, 生物标志物, ERK/JNK通路

Abstract:

Objective To investigate the expression of parathyroid hormone-like hormone (PTHLH) in hepatocellular carcinoma (HCC) and analyze its correlation with clinical prognosis, its regulatory effects on HCC cell behaviors, and the signaling pathways mediating its effects. Methods We analyzed the differential expression of PTHLH in HCC and adjacent tissues and its association with patient prognosis based on data from TCGA and GEO databases and from 70 HCC patients treated in our hospital. The effects of PTHLH knockdown and overexpression on proliferation, migration, and invasion of cultured HCC cells were investigated using CCK-8 assay, colony formation assay, Transwell migration and invasion assays, and the signaling pathways activated by PTHLH were detected using Western blotting. Results TCGA and GEO database analysis showed significant overexpression of PTHLH mRNA in HCC tissues, which was associated with poor prognosis of the patients (P<0.05). High PTHLH mRNA expression was a probable independent prognostic risk factor for HCC (P<0.05). In the clinical samples, PTHLH mRNA and protein expressions were significantly higher in HCC tissues than in the adjacent tissues (P<0.001 or 0.01). Univariate and multivariate Cox regression analyses suggested that high PTHLH mRNA expression was an independent risk factor to affect postoperative disease-free survival of HCC patients (P<0.05). The prognostic prediction model based on PTHLH mRNA expression showed an improved accuracy for predicting the risk of postoperative recurrence in HCC patients. In cultured HCC cells, PTHLH overexpression significantly promoted cell proliferation, colony formation, migration and invasion, and caused activation of the ERK/JNK signaling pathway in Huh7 and Hep3B cells. Conclusion High PTHLH expression promotes HCC progression and is associated with poor patient prognosis. Its pro-tumor effects may be mediated by activation of the ERK/JNK signaling pathway.

Key words: hepatocellular carcinoma, parathyroid hormone-like hormone, clinical prognosis, biomarker, ERK/JNK pathway