Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 27, 2024; 16(6): 932-950
Published online Jun 27, 2024. doi: 10.4254/wjh.v16.i6.932
Diagnostic and prognostic role of LINC01767 in hepatocellular carcinoma
Li Zhang, Tong-Xing Cui, Xiang-Zhi Li, Chong Liu, Wen-Qin Wang
Li Zhang, Department of Thyroid and Breast Surgery, The Affiliated People Hospital of Second Medical University, Weifang 266010, Shandong Province, China
Tong-Xing Cui, Department of General Surgery, Qingdao Municipal Hospital Group, Qingdao 266237, Shandong Province, China
Xiang-Zhi Li, Wen-Qin Wang, School of Life Sciences, Shandong University (Qingdao), Qingdao 26637, Shandong Province, China
Chong Liu, School of Medicine, Tsinghua University, Beijing 100084, China
Co-first authors: Li Zhang and Tong-Xing Cui.
Author contributions: Zhang L and Cui TX contributed equally to this work and should be considered co-first authors. Wang WQ conceived this study and implemented the experiments; Li XZ and Liu C collected and preprocessed the data; Zhang L and Wang WQ drafted and revised the manuscript.
Supported by Foundation of Qingdao Postdoctoral Innovation Project, No. QDBSH20230101019; and Funded State Key Laboratory of Marine Food Processing & Safety Control, Qingdao, No. SKL2023M05.
Institutional review board statement: The study was approved by the Ethical Review Committee of Qingdao Municipal Hospital College, No. QDSSLYY2023CB22.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset were available from the corresponding author at wenqinwangsdu@163.com.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wen-Qin Wang, MMed, Postdoc, Researcher, School of Life Sciences, Shandong University (Qingdao), No. 72 of Binhai Road, Jimo District, Qingdao 26637, Shandong Province, China. wenqinwangsdu@163.com
Received: January 23, 2024
Revised: April 8, 2024
Accepted: April 28, 2024
Published online: June 27, 2024
Processing time: 148 Days and 17.6 Hours
Abstract
BACKGROUND

Hepatocellular carcinoma (HCC) is a primary contributor to cancer-related mortality on a global scale. However, the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs are emerging markers for HCC diagnosis, prognosis, and therapeutic target. No study of LINC01767 in HCC was published.

AIM

To conduct a multi-omics analysis to explore the roles of LINC01767 in HCC for the first time.

METHODS

DESeq2 Package was used to analyze different gene expressions. Receiver operating characteristic curves assessed the diagnostic performance. Kaplan-Meier univariate and Cox multivariate analyses were used to perform survival analysis. The least absolute shrinkage and selection operator (LASSO)-Cox was used to identify the prediction model. Subsequent to the validation of LINC01767 expression in HCC fresh frozen tissues through quantitative real time polymerase chain reaction, next generation sequencing was performed following LINC01767 over expression (GSE243371), and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes/Gene Set Enrichment Analysis/ingenuity pathway analysis was carried out. In vitro experiment in Huh7 cell was carried out.

RESULTS

LINC01767 was down-regulated in HCC with a log fold change = 1.575 and was positively correlated with the cancer stemness. LINC01767 was a good diagnostic marker with area under the curve (AUC) [0.801, 95% confidence interval (CI): 0.751-0.852, P = 0.0106] and an independent predictor for overall survival (OS) with hazard ratio = 1.899 (95%CI: 1.01-3.58, P = 0.048). LINC01767 nomogram model showed a satisfied performance. The top-ranked regulatory network analysis of LINC01767 showed the regulation of genes participating various pathways. LASSO regression identified the 9-genes model showing a more satisfied performance than 5-genes model to predict the OS with AUC > 0.75. LINC01767 was down-expressed obviously in tumor than para-tumor tissues in our cohort as well as in cancer cell line; the over expression of LINC01767 inhibit cell proliferation and clone formation of Huh7 in vitro.

CONCLUSION

LINC01767 was an important tumor suppressor gene in HCC with good diagnostic and prognostic performance.

Keywords: Hepatocellular carcinoma, LINC01767, Multi-omics analysis, GSE243371, Cell proliferation, Clone formation

Core Tip: LINC01767 was down-regulated based on The Cancer Genome Atlas and GSE dataset. It was positively with the cancer stemness in hepatocellular carcinoma (HCC) based on the single cell sequence data. LINC01767 demonstrate a good diagnostic and diagnostic performance. The 9-gene model demonstrated better performance than the 5-gene model in predicting the overall survival of HCC patients using least absolute shrinkage and selection operator regression, with an area under the curve greater than 0.75. LINC01767 was down regulated obviously in tumor than para-tumor tissues in our cohort. LINC01767 was down regulated in cancer cell line comparing with LO2; the over expression of LINC01767 inhibit the cell proliferation and impede the clone formation of Huh7 in vitro.