The Prognostic Significance of CTSV Expression in Patients with Hepatocellular Carcinoma.

IF 2.1 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL
International Journal of General Medicine Pub Date : 2024-10-23 eCollection Date: 2024-01-01 DOI:10.2147/IJGM.S467179
Yuping He, Minghao Xu, Chenhao Zhou, Qiongzhu Dong, Zhiqiu Hu, Ning Ren
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引用次数: 0

Abstract

Purpose: Cathepsin V (CTSV) is a cysteine protease peptidase, which is typically upregulated in cancer and is associated with various oncogenic processes, such as angiogenesis, proliferation, apoptosis, and invasion. The study explored the role of CTSV in hepatocellular carcinoma (HCC) and its potential as a potential biomarker.

Patients and methods: This study collected tumor and peritumoral archived specimens from 180 HCC patients who underwent surgical resection at Zhongshan Hospital, Fudan University (Shanghai, China) between 2009 and 2010. We extracted data from the TCGA and GEO databases and conducted differential expression analysis, univariate Cox regression, and Kaplan-Meier analysis. Ultimately, we determined that CTSV may emerge as a potential biomarker. Then, immunohistochemical staining for CTSV was performed on tumors and adjacent tissues of HCC patients, and a Cox proportional hazards model was constructed to evaluate the prognostic significance of CTSV expression levels. Applied functional enrichment analysis to reveal the underlying molecular mechanisms. Utilized ssGSEA enrichment analysis and TIMER2.0 algorithm to explore the correlation between CTSV expression and immune cells in HCC. In vitro and in vivo experiments were conducted using human liver cancer cell lines to further validate the clinical application value of CTSV.

Results: In this study, we observed that CTSV expression was notably elevated in HCC (P < 0.001), and identified a significant association between elevated CTSV expression and reduced overall survival rates in patients. In vitro and in vivo experiments indicated that CTSV knockdown could significantly inhibit the proliferation, migration, and invasion of liver cancer cells, and it was found that the combination of CTSV knockdown with PD-1 inhibitors might enhance the therapeutic effect of PD-1 inhibitors in HCC.

Conclusion: CTSV serves as a standalone negative prognostic indicator and possesses clinical significance in HCC.

肝细胞癌患者 CTSV 表达的预后意义
目的:Cathepsin V(CTSV)是一种半胱氨酸蛋白酶肽酶,通常在癌症中上调,与血管生成、增殖、凋亡和侵袭等各种致癌过程有关。本研究探讨了 CTSV 在肝细胞癌(HCC)中的作用及其作为潜在生物标志物的潜力:本研究收集了 2009 年至 2010 年期间在复旦大学附属中山医院(中国上海)接受手术切除的 180 例 HCC 患者的肿瘤和瘤周存档标本。我们从 TCGA 和 GEO 数据库中提取了数据,并进行了差异表达分析、单变量 Cox 回归和 Kaplan-Meier 分析。最终,我们认为CTSV可能成为一种潜在的生物标志物。随后,我们对 HCC 患者的肿瘤和邻近组织进行了 CTSV 免疫组化染色,并构建了 Cox 比例危险度模型来评估 CTSV 表达水平的预后意义。应用功能富集分析揭示潜在的分子机制。利用ssGSEA富集分析和TIMER2.0算法探讨HCC中CTSV表达与免疫细胞的相关性。利用人体肝癌细胞系进行体外和体内实验,进一步验证CTSV的临床应用价值:在这项研究中,我们观察到 CTSV 在 HCC 中的表达明显升高(P < 0.001),并发现 CTSV 表达升高与患者总生存率降低之间存在显著关联。体外和体内实验表明,CTSV敲除可显著抑制肝癌细胞的增殖、迁移和侵袭,研究还发现,CTSV敲除与PD-1抑制剂联合使用可增强PD-1抑制剂对HCC的治疗效果:结论:CTSV是一个独立的阴性预后指标,在HCC中具有临床意义。
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来源期刊
International Journal of General Medicine
International Journal of General Medicine Medicine-General Medicine
自引率
0.00%
发文量
1113
审稿时长
16 weeks
期刊介绍: The International Journal of General Medicine is an international, peer-reviewed, open access journal that focuses on general and internal medicine, pathogenesis, epidemiology, diagnosis, monitoring and treatment protocols. The journal is characterized by the rapid reporting of reviews, original research and clinical studies across all disease areas. A key focus of the journal is the elucidation of disease processes and management protocols resulting in improved outcomes for the patient. Patient perspectives such as satisfaction, quality of life, health literacy and communication and their role in developing new healthcare programs and optimizing clinical outcomes are major areas of interest for the journal. As of 1st April 2019, the International Journal of General Medicine will no longer consider meta-analyses for publication.
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