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

Abstract

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.

A Ferroptosis-Related LncRNA Signature Associated with Prognosis, Tumor Immune Environment, and Genome Instability in Hepatocellular Carcinoma

“…To further evaluate the FRlncRNA signature, we compared our risk model with reported risk models based on immune- or ferroptosis-related lncRNAs to predict prognosis of HCC. The formulae to calculate risk scores were retrieved from the publications and recalculated in our dataset [ 34 – 36 ]. Our signature showed better prediction ability (AUC = 0.779) compared to other three models (AUC = 0.729, 0.750 and 0.764) (Figure S1 ).…”

Long non-coding RNA LINC00152 in cancer: Roles, mechanisms, and chemotherapy and radiotherapy resistance

“…Similarly, Ji et al ( 21 ) showed that LINC00152 could activate the mammalian target of rapamycin (mTOR) signaling pathway through a combination of EpCAM promoters in a cis-regulated manner, which promotes HCC cell proliferation in vitro and tumor growth in vivo ( 21 ). In hepatocellular cancer, a signature of immunoautophagy-related lncRNA (IAR-lncRNA) predicts survival ( 27 ). LINC00152 can be used as a biomarker for the differential diagnosis of liver cancer ( 20 ).…”

“…Hu et al (25) reported that interfering with LINC00152 can inhibit proliferation, arrest the cell cycle, and promote apoptosis of hepatocellular cancer cells by regulating the miR-125b-5p/ KIAA1522 axis (25). Wang et al (26) demonstrated that silencing LINC00152 inhibited HCC development by modulating miR-215 to upregulate CDK13 (26). Deng et al (24) found that HBx enhances the expression of LINC00152 and promotes the proliferation and invasion of HCC cells (24).…”

An Immune-Related Long Noncoding RNA Pair as a New Biomarker to Predict the Prognosis of Patients in Breast Cancer

“…Meanwhile, some studies have shown that tumor-related lncRNAs could also participate in changing the inherent properties of tumor cells and the expression of immune genes to remodel the tumor immune microenvironment ( Eptaminitaki et al, 2021 ). For example, LINC0187 could affect the prognosis of endometrial cancer, whose high expression may indicate a better prognosis ( Wang Z. et al, 2021 ); the immune-autophagy-related lncRNA signatures including MIR210HG, AC09985.3 and CYTOR as unfavorable prognostic determinants could exhibit a predictive ability in hepatocellular carcinoma (HCC) ( Wang Y. et al, 2021 ); lncRNA including major histocompatibility complex-I (MHC-I) and immunogenicity of tumor (LIMIT) could boost guanylate-binding proteins (GBPs) and MHC-1 to enhance tumor immunogenicity and checkpoint therapy, and the LIMIT-GBP-heat shock factor-1 (HSF1) axis might be a target of cancer immunotherapy ( Li G. et al, 2021 ). However, there are few studies on the association between lncRNAs and BRCA immune microenvironment, and the prognostic value of irlncRNAs in BRCA remains unclear recently.…”