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PAXIP1受NRF1调控,是肝细胞癌中与预后相关的生物标志物。

PAXIP1 is regulated by NRF1 and is a prognosis‑related biomarker in hepatocellular carcinoma.

作者信息

Cheng Qian, Han Xiao, Xie Hao, Liao Yan-Lin, Wang Fei, Cui Xiao-Ying, Jiang Chao, Zhang Cheng-Wan

机构信息

Department of Pathogen Biology, Microbiology Division, Key Laboratory of Pathogen of Jiangsu Province Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.

Department of Central Laboratory, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China.

出版信息

Biomed Rep. 2024 Dec 22;22(3):38. doi: 10.3892/br.2024.1916. eCollection 2025 Mar.

DOI:10.3892/br.2024.1916
PMID:39781045
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11704871/
Abstract

Hepatocellular carcinoma (HCC) is characterized by a poor prognosis globally. PAX-interacting protein 1 (PAXIP1) serves a key role in the development of numerous human cancer types. Nevertheless, its specific involvement in HCC remains poorly understood. Public repository systems (Integrative Molecular Database of HCC, Gene Expression Omnibus, The Cancer Genome Atlas, University of Alabama at Birmingham Cancer Data Analysis Portal, Tumor Immune Estimation Resource and Human Protein Atlas) were utilized to explore PAXIP1 expression in HCC and evaluate the prognostic value of PAXIP1 in patients with HCC. PAXIP1 expression was investigated, and a notable relationship between PAXIP1 expression and various cancer types was found through analysis of The Cancer Genome Atlas data. More specifically, patients with HCC and lower PAXIP1 levels had improved survival rates. Furthermore, using LinkedOmics, the co-expression network of PAXIP1 in HCC was determined. Colocalization analysis of PAXIP1 using chromatin immunoprecipitation-sequencing data suggested that PAXIP1 might act as a cofactor for MYB proto-oncogene like 2 or FOXO1 in HCC. In addition, by predicting and analyzing the potential transcription factors related to PAXIP1, nuclear respiratory factor 1 was identified as a factor upstream of PAXIP1 in HCC. Notably, PAXIP1 expression exhibited a positive association with the infiltration of CD4 and CD8 T cells, macrophages, neutrophils and myeloid dendritic cells. Furthermore, PAXIP1 expression was associated with a range of immune markers such as programmed cell death protein 1, programmed death-ligand 1 and cytotoxic T-lymphocyte associated protein 4 in HCC. The findings of the present study highlighted the prognostic relevance of PAXIP1 and its function in modulating immune cell recruitment in HCC.

摘要

肝细胞癌(HCC)在全球范围内具有预后不良的特征。PAX相互作用蛋白1(PAXIP1)在多种人类癌症类型的发生发展中起关键作用。然而,其在HCC中的具体作用仍知之甚少。利用公共数据库系统(HCC综合分子数据库、基因表达综合数据库、癌症基因组图谱、阿拉巴马大学伯明翰分校癌症数据分析门户、肿瘤免疫评估资源和人类蛋白质图谱)来探索PAXIP1在HCC中的表达,并评估PAXIP1对HCC患者的预后价值。研究了PAXIP1的表达,并通过分析癌症基因组图谱数据发现了PAXIP1表达与各种癌症类型之间的显著关系。更具体地说,PAXIP1水平较低的HCC患者生存率有所提高。此外,使用LinkedOmics确定了HCC中PAXIP1的共表达网络。利用染色质免疫沉淀测序数据对PAXIP1进行共定位分析表明,PAXIP1可能在HCC中作为MYB原癌基因样2或FOXO1的辅因子发挥作用。此外,通过预测和分析与PAXIP1相关的潜在转录因子,核呼吸因子1被确定为HCC中PAXIP1上游的一个因子。值得注意的是,PAXIP1表达与CD4和CD8 T细胞、巨噬细胞、中性粒细胞和髓样树突状细胞的浸润呈正相关。此外,PAXIP1表达与HCC中的一系列免疫标志物如程序性细胞死亡蛋白1、程序性死亡配体1和细胞毒性T淋巴细胞相关蛋白4有关。本研究结果突出了PAXIP1的预后相关性及其在调节HCC免疫细胞募集方面的功能。

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