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DNAJC7表达增加通过影响细胞周期和免疫微环境促进肝细胞癌进展。

Increased expression of DNAJC7 promotes the progression of hepatocellular carcinoma by influencing the cell cycle and immune microenvironment.

作者信息

Chen Jiaxing, Yang Zhizhao, Cui Yongqiang, Zhao Zhilei, Deng Dongfeng, Fu Zhihao, Zhang Xiao

机构信息

Department of Hepatobiliary Pancreatic Surgery, Henan Provincial People's Hospital, Zhengzhou City, 450003, Henan Province, China.

Hepatobiliary Pancreatic Surgery Department of Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou City, 450003, Henan Province, China.

出版信息

J Cancer Res Clin Oncol. 2025 May 2;151(5):154. doi: 10.1007/s00432-025-06202-0.

DOI:10.1007/s00432-025-06202-0
PMID:40312488
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12045834/
Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related mortality worldwide owing to the lack of effective and early diagnostic tools and therapeutic approaches. DNAJC7, a member of the DnaJ heat shock family, is crucial in protein folding and stability; however, its specific functions and mechanisms in HCC remain unclear.

OBJECTIVE

This study aimed to explore the role of DNAJC7 in HCC progression and evaluate its potential clinical significance as a prognostic marker.

METHODS

Public databases (TCGA, ICGC, GEO, and TIMER) were used to assess DNAJC7 expression, correlations with clinical parameters, and related signaling pathways. Proliferation, migration, invasion, and cell cycle assays were performed to evaluate the function of DNAJC7 in HCC. Immune infiltration and associations with checkpoint proteins were analyzed using TIMER, and a Gene Set Enrichment Analysis (GSEA) was used to explore enriched pathways.

RESULTS

DNAJC7 expression was higher in HCC tissues than in adjacent normal tissues and was associated with advanced malignancy and poor prognosis, including a lower overall survival, progression-free survival, and disease-free survival. DNAJC7 knockdown resulted in reduced malignant behavior of HCC cells, leading to S-phase cell cycle arrest. Increased DNAJC7 expression was associated with immune cell infiltration and the presence of immunological checkpoint molecules, including CTLA4 and PD-1. GSEA highlighted the activation of key pathways, including WNT signaling and cell cycle regulation.

CONCLUSION

DNAJC7 regulates tumor cell proliferation, migration, invasion, and immune evasion by acting as an oncogene in HCC. It can serve as a diagnostic and prognostic biomarker and potential treatment target for HCC.

摘要

背景

由于缺乏有效的早期诊断工具和治疗方法,肝细胞癌(HCC)是全球癌症相关死亡的主要原因。DNAJC7是DnaJ热休克家族的成员,在蛋白质折叠和稳定性方面至关重要;然而,其在HCC中的具体功能和机制仍不清楚。

目的

本研究旨在探讨DNAJC7在HCC进展中的作用,并评估其作为预后标志物的潜在临床意义。

方法

使用公共数据库(TCGA、ICGC、GEO和TIMER)评估DNAJC7的表达、与临床参数的相关性以及相关信号通路。进行增殖、迁移、侵袭和细胞周期分析以评估DNAJC7在HCC中的功能。使用TIMER分析免疫浸润以及与检查点蛋白的关联,并使用基因集富集分析(GSEA)探索富集的通路。

结果

HCC组织中DNAJC7的表达高于相邻正常组织,并且与晚期恶性肿瘤和不良预后相关,包括较低的总生存期、无进展生存期和无病生存期。DNAJC7敲低导致HCC细胞的恶性行为减少,导致S期细胞周期停滞。DNAJC7表达增加与免疫细胞浸润以及免疫检查点分子(包括CTLA4和PD-1)的存在相关。GSEA突出了关键通路的激活,包括WNT信号传导和细胞周期调节。

结论

DNAJC7在HCC中作为癌基因调节肿瘤细胞的增殖、迁移、侵袭和免疫逃逸。它可以作为HCC的诊断和预后生物标志物以及潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/12045834/677ac5366e45/432_2025_6202_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/12045834/a0aa36e1d4ea/432_2025_6202_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/12045834/677ac5366e45/432_2025_6202_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/12045834/3e3f65b220a2/432_2025_6202_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/12045834/0ed71f5376ea/432_2025_6202_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/12045834/7074d6f5daea/432_2025_6202_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/12045834/ac5b52d406dd/432_2025_6202_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/12045834/b3711b0d9919/432_2025_6202_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/12045834/a0aa36e1d4ea/432_2025_6202_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/adb6/12045834/677ac5366e45/432_2025_6202_Fig8_HTML.jpg

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本文引用的文献

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Tumour heterogeneity and personalized treatment screening based on single-cell transcriptomics.基于单细胞转录组学的肿瘤异质性与个性化治疗筛选
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A protein expression atlas on tissue samples and cell lines from cancer patients provides insights into tumor heterogeneity and dependencies.癌症患者的组织样本和细胞系的蛋白质表达图谱提供了对肿瘤异质性和依赖性的深入了解。
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