通过广泛的数据库检索发现，高 HBXIP 表达与 HCC 的不良预后相关。

High HBXIP expression is related to poor prognosis in HCC by extensive database interrogation.

机构信息

Department of Radiology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.

出版信息

Eur Rev Med Pharmacol Sci. 2021 Oct;25(20):6196-6207. doi: 10.26355/eurrev_202110_26990.

DOI:10.26355/eurrev_202110_26990

PMID:34730200

Abstract

OBJECTIVE

The involvement of HBXIP in cancer development and cancer cell survival is well known. This work probed the potential of HBXIP as a prognostic biomarker in hepatic cell cancer (HCC).

MATERIALS AND METHODS

First, pan-cancer analysis of HBXIP expression was conducted using The Cancer Genome Atlas (TCGA) database to validate the expression of HBXIP in different cancers. The GSE14520 (GPL3721 Subset) database was used to validate HBXIP in HCC. The association between survival outcomes and prognostic factors was assessed employing univariate and multivariate survival analyses for TCGA Liver Hepatocellular Carcinoma. The biological function of the HBXIP Gene was annotated by gene set enrichment analysis. The relationship between HBXIP expression and immune cells and immune markers was analyzed from the Gene Expression Profiling Interactive Analysis (GEPIA) database.

RESULTS

Malignant tissues demonstrated evident upregulation of HBXIP at transcriptional and protein levels over normal tissues (p < 0.05) with this elevated expression linked to an advanced tumor stage in HCC cohorts. Univariate analysis revealed an evident correlation emerged between prognosis and HBXIP for GSE14520 databases (p < 0.05). The disease-free survival (DFS) and overall survival (OS) (five-year values) were lower in samples demonstrating elevated HBXIP (HR: 2.413; 95% CI 1.601, 3.638; p < 0.001) and (HR: 1.613; 95% CI 1.446, 1.844; p = 0.003), respectively vs. lower HBXIP expression. HBXIP emerged as an independent factor in OS prognosis (HR 2.184; 95% CI 1.495, 3.196; p < 0.001) and DFS (HR 1.764; 95% CI 1.261, 2.466; p < 0.001), respectively according to multivariate analysis. Further, multiple Cox analyses in the validation cohort revealed that independent factors for OS were HBXIP, AJCC T stage, vascular invasion, and tumor status with the C-index score of 0.727 (95% CI, 0.704 to 0.750). HBXIP level showed a significantly positive association with tumor immune cell infiltration, and biomarkers of immune cells; besides, the rectum Rho GTPase effectors signaling pathway was also identified.

CONCLUSIONS

HCC advancement and survival involves HBXIP, which also emerged as a functional biomarker for HCC survival prediction.

摘要

目的

HBXIP 参与癌症的发生和癌细胞的存活已得到充分证实。本研究旨在探讨 HBXIP 作为肝细胞癌（HCC）预后标志物的潜力。

材料与方法

首先，利用癌症基因组图谱（TCGA）数据库进行泛癌症分析，以验证 HBXIP 在不同癌症中的表达情况。采用 GSE14520（GPL3721 子集）数据库验证 HCC 中的 HBXIP。通过 TCGA 肝肝细胞癌的单变量和多变量生存分析评估生存结果与预后因素之间的关联。通过基因集富集分析注释 HBXIP 基因的生物学功能。从基因表达谱交互分析（GEPIA）数据库分析 HBXIP 表达与免疫细胞和免疫标志物的关系。

结果

与正常组织相比，恶性组织在转录和蛋白水平上均明显上调 HBXIP（p < 0.05），并且在 HCC 队列中，这种高表达与肿瘤晚期有关。单变量分析显示，GSE14520 数据库中预后与 HBXIP 之间存在明显相关性（p < 0.05）。与 HBXIP 低表达相比，HBXIP 升高的样本的无病生存期（DFS）和总生存期（OS）（五年值）较低（HR：2.413；95%CI 1.601，3.638；p < 0.001）和（HR：1.613；95%CI 1.446，1.844；p = 0.003）。HBXIP 是 OS 预后的独立因素（HR 2.184；95%CI 1.495，3.196；p < 0.001）和 DFS（HR 1.764；95%CI 1.261，2.466；p < 0.001），分别根据多变量分析。进一步，在验证队列中的多项 Cox 分析显示，OS 的独立因素为 HBXIP、AJCC T 分期、血管侵犯和肿瘤状态，C 指数评分为 0.727（95%CI，0.704 至 0.750）。HBXIP 水平与肿瘤免疫细胞浸润和免疫细胞标志物呈显著正相关；此外，还确定了直肠 Rho GTP 酶效应物信号通路。