Abstract
Abnormally expressed long noncoding RNAs (lncRNAs) have been reported to affect the occurrence and progression of hepatocellular carcinoma (HCC) by modulating the autophagy axis. However, none of studies has explored the clinical significance of these autophagy-related lncRNAs in HCC comprehensively. In this study, the RNA-seq, miRNA-seq, and clinical data of normal and HCC patients from the TCGA database and autophagy genes from the Human Autophagy Database were extracted. Subsequently, we screened out 78 differentially expressed autophagy-related lncRNAs, and four prognostic-related lncRNAs (LUCAT1, AC099850.3, ZFPM2-AS1, and AC009005.1) were eventually used to develop the prognostic model. This signature could be regarded as an independent prognostic signature for HCC patients and has the highest prediction efficiency than other clinicopathological factors for the 1-, 3-, and 5-year survival (AUC = 0.764, 0.738, and 0.717, respectively). Additionally, regardless of whether the clinical information is complete for HCC patients, the autophagy-related lncRNA model shows a good predictive power for the overall survival. Importantly, the coexpression network of 4 lncRNAs and 11 autophagy-related genes was constructed. Moreover, based on the bioinformatic analyses, our results found that LUCAT1 and ZFPM2-AS1 may affect the autophagic activity in HCC through the hsa-miR-495-3p/DLC1 and hsa-miR-515-5p/DAPK2 axis, respectively. In conclusion, we establish an effective prognostic model for HCC patients and shed new light on the autophagy-related regulatory mechanisms of the identified lncRNAs.
Highlights
Hepatocellular carcinoma (HCC) is the most frequent liver tumor, accounting for 75–80% of all primary liver cancer cases and arises from chronic liver inflammation and liver fibrosis mostly [1, 2]
To retrieve the required long noncoding RNAs (lncRNAs) expression information using Homo sapiens’ ensemble ID, the 14370 lncRNA expression profiles were included in the study
The expression data of these autophagy-related genes were extracted from TCGA, which were used for further identifying their relationship with differentially expressed lncRNAs
Summary
Hepatocellular carcinoma (HCC) is the most frequent liver tumor, accounting for 75–80% of all primary liver cancer cases and arises from chronic liver inflammation and liver fibrosis mostly [1, 2]. Despite the major progress in risk factors, early diagnosis, and treatment techniques for HCC, the poor prognosis of HCC patients remains unsatisfactory (overall mortality to incidence rate, 0.95) [2]. Because of the complex molecular mechanisms and high cellular heterogeneity of HCC patients, traditional clinical parameters including AFP, TNM stage, and vascular invasion have the limited predictive power. New and more accurate methods with a better understanding of the underlying HCC development mechanisms are urgently needed to facilitate early detection, help prognostic prediction, and guide individualized treatment. Dysregulation of the autophagic process has been reported to regulate a variety of pathological conditions and cancer development, including HCC [5,6,7]. The function of autophagy in HCC is a hotspot, and the autophagy process can play either a protective or a detrimental role in the occurrence and development of HCC
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