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脯氨酰3-羟化酶1在肝细胞癌中的预后意义及潜在机制

The Prognostic Significance and Potential Mechanism of Prolyl 3-Hydroxylase 1 in Hepatocellular Carcinoma.

作者信息

Li Chunlei, Zhang Lilong, Xu Yao, Chai Dongqi, Nan Shengchen, Qiu Zhendong, Wang Weixing, Deng Wenhong

机构信息

Department of General Surgery, Renmin Hospital of Wuhan University, No.238, Jiefang Road, Wuchang District, Wuhan 430060, Hubei Province, China.

Hubei Key Laboratory of Digestive System Disease, No.238, Jiefang Road, Wuchang District, Wuhan 430060, Hubei Province, China.

出版信息

J Oncol. 2022 Oct 26;2022:7854297. doi: 10.1155/2022/7854297. eCollection 2022.

DOI:10.1155/2022/7854297
PMID:36339646
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9629929/
Abstract

BACKGROUND

Prolyl 3-hydroxylase 1 (P3H1) is essential for human collagen synthesis. Here, we investigated its relevance to multiple cancers, especially hepatocellular carcinoma (LIHC).

METHODS

We estimated the relationship of P3H1 with 33 cancers using publicly available databases. And immunohistochemistry was utilized to verify the P3H1 expression in liver, gastric, colon, pancreatic, and rectal cancer. Then, we attenuated P3H1 expression in BEL-7402 and HLF cells by lentivirus technology and assessed the effect of P3H1 on cell proliferation, migration, and invasion.

RESULTS

Bioinformatic analysis revealed a significantly higher expression of P3H1 in almost all tumors, which was consistent with the immunohistochemical findings in the liver, gastric, colon, pancreatic, and rectal cancers. P3H1 expression was associated with overall survival, progression-free interval, disease-specific survival, and disease-free interval in most cancers, particularly in LIHC. Besides, we also found that P3H1 expression was an independent prognostic factor for LIHC. And knockdown of P3H1 significantly reduced liver cancer cell proliferation, migration, and invasion in liver cancer cells. Interestingly, P3H1 expression levels showed a significant positive connection with Th2 infiltration through multiple immune infiltration algorithms. ICI treatment was less effective in LIHC patients with high P3H1 expression. Finally, we also identified an upstream regulatory mechanism of P3H1 in LIHC, namely, AL355488.1, HCG18, and THUMPD3-AS1/hsa-miR-29c-3p-P3H1 axis.

CONCLUSION

We have systematically described for the first time that P3H1 is closely related to various tumors, particularly in LIHC, and interference with P3H1 may be a therapeutic target for patients with LIHC.

摘要

背景

脯氨酰3-羟化酶1（P3H1）对人类胶原蛋白合成至关重要。在此，我们研究了其与多种癌症的相关性，尤其是肝细胞癌（LIHC）。

方法

我们使用公开可用的数据库评估了P3H1与33种癌症的关系。并利用免疫组织化学法验证P3H1在肝癌、胃癌、结肠癌、胰腺癌和直肠癌中的表达。然后，我们通过慢病毒技术在BEL-7402和HLF细胞中降低P3H1的表达，并评估P3H1对细胞增殖、迁移和侵袭的影响。

结果

生物信息学分析显示，几乎所有肿瘤中P3H1的表达均显著升高，这与肝癌、胃癌、结肠癌、胰腺癌和直肠癌的免疫组织化学结果一致。在大多数癌症中，尤其是在LIHC中，P3H1表达与总生存期、无进展生存期、疾病特异性生存期和无病生存期相关。此外，我们还发现P3H1表达是LIHC的独立预后因素。敲低P3H1可显著降低肝癌细胞的增殖、迁移和侵袭能力。有趣的是，通过多种免疫浸润算法，P3H1表达水平与Th2浸润呈显著正相关。P3H1高表达的LIHC患者接受免疫检查点抑制剂（ICI）治疗效果较差。最后，我们还确定了LIHC中P3H1的上游调控机制，即AL355488.1、HCG18和THUMPD3-AS1/hsa-miR-29c-3p-P3H1轴。

结论

我们首次系统地描述了P3H1与各种肿瘤密切相关，尤其是在LIHC中，干扰P3H1可能是LIHC患者的治疗靶点。

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