长链非编码RNA ZFHX4-AS1作为肾上腺皮质癌的一种新型生物标志物

LncRNA ZFHX4-AS1 as a novel biomarker in adrenocortical carcinoma.

作者信息

Chen Guo, Li Songbo, Lu Jianming, Liang Anyun, Gao Ping, Ou Fengmeng, Wang Yu, Li Yutong, Pan Bin

机构信息

Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, China.

Department of Andrology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.

出版信息

Transl Androl Urol. 2024 Jul 31;13(7):1188-1205. doi: 10.21037/tau-23-649. Epub 2024 Jul 16.

DOI:10.21037/tau-23-649

PMID:39100837

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11291411/

Abstract

BACKGROUND

Adrenocortical carcinoma (ACC) is a rare and highly aggressive malignant tumor. Currently, there is a lack of reliable prognostic markers in clinical practice. Extensive research has shown that long non-coding RNA (lncRNA) are critical factors in the initiation and progression of cancer, closely associated with early diagnosis and prognosis. Previous studies have identified that ZFHX4 antisense RNA 1 (ZFHX4-AS1) is aberrantly expressed in various cancers and is associated with poor outcomes. This study investigates whether ZFHX4-AS1 affects the prognosis of ACC patients and, if so, the potential mechanisms involved.

METHODS

In this study, utilizing four multi-center cohorts from The Cancer Genome Atlas (TCGA) program and Gene Expression Omnibus (GEO), we validated the prognostic capability of ZFHX4-AS1 in ACC patients through Kaplan-Meier survival analysis, cox regression models, and nomograms. Then, we explored the biological functions of ZFHX4-AS1 using gene set enrichment analysis (GSEA), competing endogenous RNA (ceRNA) networks, and analyses of somatic mutations and copy number variation (CNV). Finally, experiments were conducted to further validate the impact of ZFHX4-AS1 on proliferation and migration capabilities of ACC cell lines.

RESULTS

Survival analysis indicated that patients in the high ZFHX4-AS1 expression group of ACC had worse prognosis. Cox regression analyses suggested that ZFHX4-AS1 levels were independent risk factors for prognosis. Subsequently, we constructed nomograms based on clinical features and ZFHX4-AS1 levels, demonstrating good predictive performance under the time-dependent receiver operating characteristic (ROC) curve. Analysis based on somatic mutations and CNV revealed that CTNNB1 and 9p21.3-Del drove the expression of ZFHX4-AS1. Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays confirmed that knockdown of ZFHX4-AS1 inhibited proliferation and migration of ACC cells.

CONCLUSIONS

This study demonstrates that ZFHX4-AS1 has a reliable predictive value for the prognosis of ACC patients and is a promising biomarker.

摘要

背景

肾上腺皮质癌（ACC）是一种罕见且侵袭性很强的恶性肿瘤。目前，临床实践中缺乏可靠的预后标志物。广泛的研究表明，长链非编码RNA（lncRNA）是癌症发生和发展的关键因素，与早期诊断和预后密切相关。先前的研究已确定锌指同源盒4反义RNA 1（ZFHX4-AS1）在多种癌症中异常表达，并与不良预后相关。本研究调查ZFHX4-AS1是否影响ACC患者的预后，若有影响，其潜在机制是什么。

方法

在本研究中，我们利用来自癌症基因组图谱（TCGA）计划和基因表达综合数据库（GEO）的四个多中心队列，通过Kaplan-Meier生存分析、Cox回归模型和列线图验证ZFHX4-AS1对ACC患者的预后评估能力。然后，我们使用基因集富集分析（GSEA）、竞争性内源RNA（ceRNA）网络以及体细胞突变和拷贝数变异（CNV）分析来探索ZFHX4-AS1的生物学功能。最后，进行实验进一步验证ZFHX4-AS1对ACC细胞系增殖和迁移能力的影响。

结果

生存分析表明，ACC患者中ZFHX4-AS1高表达组的预后较差。Cox回归分析表明，ZFHX4-AS1水平是预后的独立危险因素。随后，我们基于临床特征和ZFHX4-AS1水平构建了列线图，在时间依赖性受试者工作特征（ROC）曲线下显示出良好的预测性能。基于体细胞突变和CNV的分析表明，β-连环蛋白（CTNNB1）和9p21.3缺失驱动了ZFHX4-AS1的表达。细胞计数试剂盒-8（CCK-8）、集落形成和Transwell实验证实，敲低ZFHX4-AS1可抑制ACC细胞的增殖和迁移。