Liang Jiaying, Zhi Yaofeng, Deng Wenhui, Zhou Weige, Li Xuejun, Cai Zheyou, Zhu Zhijian, Zeng Jinxiang, Wu Wanlan, Dong Ying, Huang Jin, Zhang Yuzhuo, Xu Shichao, Feng Yixin, Ding Fuping, Zhang Jin
Guangzhou University of Chinese Medicine, School of Basic Medical Sciences, Guangzhou, China.
Guangzhou University of Chinese Medicine, Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou, China.
PeerJ. 2021 Jun 11;9:e11627. doi: 10.7717/peerj.11627. eCollection 2021.
Hepatocellular carcinoma (HCC) with high heterogeneity is one of the most frequent malignant tumors throughout the world. However, there is no research to establish a ferroptosis-related lncRNAs (FRlncRNAs) signature for the patients with HCC. Therefore, this study was designed to establish a novel FRlncRNAs signature to predict the survival of patients with HCC.
The expression profiles of lncRNAs were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. FRlncRNAs co-expressed with ferroptosis-related genes were utilized to establish a signature. Cox regression was used to construct a novel three FRlncRNAs signature in the TCGA cohort, which was verified in the GEO validation cohort.
Three differently expressed FRlncRNAs significantly associated with prognosis of HCC were identified, which composed a novel FRlncRNAs signature. According to the FRlncRNAs signature, the patients with HCC could be divided into low- and high-risk groups. Patients with HCC in the high-risk group displayed shorter overall survival (OS) contrasted with those in the low-risk group ( < 0.001 in TCGA cohort and = 0.045 in GEO cohort). This signature could serve as a significantly independent predictor in Cox regression (multivariate HR > 1, < 0.001), which was verified to a certain extent in the GEO cohort (univariate HR > 1, < 0.05). Meanwhile, it was also a useful tool in predicting survival among each stratum of gender, age, grade, stage, and etiology,etc. This signature was connected with immune cell infiltration (i.e., Macrophage, Myeloid dendritic cell, and Neutrophil cell, etc.) and immune checkpoint blockade targets (PD-1, CTLA-4, and TIM-3).
The three FRlncRNAs might be potential therapeutic targets for patients, and their signature could be utilized for prognostic prediction in HCC.
具有高度异质性的肝细胞癌（HCC）是全球最常见的恶性肿瘤之一。然而，尚无研究为HCC患者建立与铁死亡相关的长链非编码RNA（FRlncRNAs）特征。因此，本研究旨在建立一种新的FRlncRNAs特征以预测HCC患者的生存情况。
从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）获取lncRNAs的表达谱。利用与铁死亡相关基因共表达的FRlncRNAs建立特征。采用Cox回归在TCGA队列中构建一个新的包含三个FRlncRNAs的特征，并在GEO验证队列中进行验证。
鉴定出三个与HCC预后显著相关的差异表达FRlncRNAs，它们构成了一个新的FRlncRNAs特征。根据该特征，HCC患者可分为低风险组和高风险组。高风险组的HCC患者总生存期（OS）短于低风险组（TCGA队列中P<0.001，GEO队列中P = 0.045）。该特征在Cox回归中可作为显著的独立预测因子（多变量HR>1，P<0.001），在GEO队列中也得到了一定程度的验证（单变量HR>1，P<0.05）。同时，它也是预测性别、年龄、分级、分期和病因等各分层患者生存情况的有用工具。该特征与免疫细胞浸润（即巨噬细胞、髓系树突状细胞和中性粒细胞等）以及免疫检查点阻断靶点（PD-1、CTLA-4和TIM-3）相关。
这三个FRlncRNAs可能是患者潜在的治疗靶点，其特征可用于HCC的预后预测。
