Immunoautophagy-Related Long Noncoding RNA (IAR-lncRNA) Signature Predicts Survival in Hepatocellular Carcinoma

Biology

Amit Sharma¹  Yulu Wang¹  Ingo G. H. Schmidt-Wolf¹  Fangfang Ge¹  Maria F. Setiawan¹  Oliver Rudan¹  Maria A. Gonzalez-Carmona²  Miroslaw T. Kornek²  Christian P. Strassburg²  Matthias Schmid³ 

[1] Center for Integrated Oncology (CIO), Department of Integrated Oncology, University Hospital of Bonn, 53127 Bonn, Germany;Department of Internal Medicine I, University Hospital of Bonn, 53127 Bonn, Germany;Institute of Medical Biometry, Informatics and Epidemiology, University Hospital of Bonn, 53127 Bonn, Germany;

关键词: liver cancer;    hepatocellular carcinoma;    lncRNAs;    autophagy;    biomarker;    kyoto encyclopedia of genes and genomes;   

DOI  :  10.3390/biology10121301

来源: DOAJ

【 摘 要 】

Background: The dysregulation of autophagy and immunological processes has been linked to various pathophysiological conditions, including cancer. Most notably, their particular involvement in hepatocellular carcinoma (HCC) is becoming increasingly evident. This has led to the possibility of developing a prognostic signature based on immuno-autophagy-related (IAR) genes. Given that long non-coding RNAs (lncRNAs) also play a special role in HCC, a combined signature utilizing IAR genes and HCC-associated long noncoding RNAs (as IARlncRNA) may potentially help in the clinical scenario. Method: We used Pearson correlation analysis, Kaplan–Meier survival curves, univariate and multivariate Cox regression, and ROC curves to generate and validate a prognostic immuno-autophagy-related long non-coding RNA (IARlncRNA) signature. The Chi-squared test was utilized to investigate the correlation between the obtained signature and the clinical characteristics. CIBERSORT algorithms and the Wilcoxon rank sum test were applied to investigate the correlation between signature and infiltrating immune cells. GO and KEGG analyses were performed to derived signature-dependent pathways. Results: Herein, we build an IAR-lncRNA signature (as first in the literature) and demonstrate its prognostic ability in hepatocellular carcinoma. Primarily, we identified three IARlncRNAs (MIR210HG, AC099850.3 and CYTOR) as unfavorable prognostic determinants. The obtained signature predicted the high-risk HCC group with shorter overall survival, and was further associated with clinical characteristics such as tumor grade (t = 10.918, p = 0.001). Additionally, several infiltrating immune cells showed varied fractions between the low-risk group and the high-risk HCC groups in association with the obtained signature. In addition, pathways analysis described by the signature clearly distinguishes both risk groups in HCC. Conclusions: The immuno-autophagy-related long non-coding RNA (IARlncRNA) signature we established exhibits a prognostic ability in hepatocellular carcinoma. To our knowledge, this is the first attempt in the literature to combine three determinants (immune, autophagy and LnRNAs), thus requiring molecular validation of this obtained signature in clinical samples.

【 授权许可】

Unknown