自噬相关特征作为肝细胞癌的预后指标
Autophagy-Related Signatures as Prognostic Indicators for Hepatocellular Carcinoma.
作者信息
Ye Wen, Shi Zhehao, Zhou Yilin, Zhang Zhongjing, Zhou Yi, Chen Bicheng, Zhang Qiyu
机构信息
Department of Breast Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
出版信息
Front Oncol. 2022 Mar 24;12:654449. doi: 10.3389/fonc.2022.654449. eCollection 2022.
BACKGROUND
Hepatocellular carcinoma (HCC) is the most common and deadly type of liver cancer. Autophagy is the process of transporting damaged or aging cellular components into lysosomes for digestion and degradation. Accumulating evidence implies that autophagy is a key factor in tumor progression. The aim of this study was to determine a panel of novel autophagy-related prognostic markers for liver cancer.
METHODS
We conducted a comprehensive analysis of autophagy-related gene (ARG) expression profiles and corresponding clinical information based on The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The univariate Cox proportional regression model was used to screen candidate autophagy-related prognostic genes. In addition, a multivariate Cox proportional regression model was used to identify five key prognostic autophagy-related genes (ATIC, BAX, BIRC5, CAPNS1, and FKBP1A), which were used to construct a prognostic signature. Real-time qPCR analysis was used to evaluate the expression levels of ARGs in 20 surgically resected HCC samples and matched tumor-adjacent normal tissue samples. In addition, the effect of FKBP1A on autophagy and tumor progression was determined by performing and experiments.
RESULTS
Based on the prognostic signature, patients with liver cancer were significantly divided into high-risk and low-risk groups in terms of overall survival (OS). A subsequent multivariate Cox regression analysis indicated that the prognostic signature remained an independent prognostic factor for OS. The prognostic signature possessing a better area under the curve (AUC) displayed better performance in predicting the survival of patients with HCC than other clinical parameters. Furthermore, FKBP1A was overexpressed in HCC tissues, and knockdown of FKBP1A impaired cell proliferation, migration, and invasion through the PI3K/AKT/mTOR signaling pathway.
CONCLUSION
This study provides a prospective biomarker for monitoring outcomes of patients with HCC.
背景
肝细胞癌（HCC）是最常见且致命的肝癌类型。自噬是将受损或老化的细胞成分运输到溶酶体中进行消化和降解的过程。越来越多的证据表明自噬是肿瘤进展的关键因素。本研究的目的是确定一组用于肝癌的新型自噬相关预后标志物。
方法
我们基于癌症基因组图谱（TCGA）和国际癌症基因组联盟（ICGC）数据库，对自噬相关基因（ARG）表达谱及相应临床信息进行了综合分析。采用单变量Cox比例回归模型筛选候选自噬相关预后基因。此外，使用多变量Cox比例回归模型鉴定了五个关键的自噬相关预后基因（ATIC、BAX、BIRC5、CAPNS1和FKBP1A），并用于构建预后特征。采用实时定量PCR分析评估20例手术切除的HCC样本及配对的肿瘤旁正常组织样本中ARG的表达水平。此外，通过进行 和 实验确定FKBP1A对自噬和肿瘤进展的影响。
结果
基于预后特征，肝癌患者在总生存期（OS）方面被显著分为高风险和低风险组。随后的多变量Cox回归分析表明，预后特征仍然是OS的独立预后因素。与其他临床参数相比，具有更好曲线下面积（AUC）的预后特征在预测HCC患者生存方面表现更佳。此外，FKBP1A在HCC组织中过表达，敲低FKBP1A可通过PI3K/AKT/mTOR信号通路损害细胞增殖、迁移和侵袭。
结论
本研究为监测HCC患者的预后提供了一种前瞻性生物标志物。
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