Development and validation of a novel cellular senescence-related prognostic signature for predicting the survival and immune landscape in hepatocellular carcinoma

Abstract

Background: Cellular senescence is a typical irreversible form of life stagnation, and recent studies have suggested that long non-coding ribonucleic acids (lncRNA) regulate the occurrence and development of various tumors. In the present study, we attempted to construct a novel signature for predicting the survival of patients with hepatocellular carcinoma (HCC) and the associated immune landscape based on senescence-related (sr) lncRNAs.Method: Expression profiles of srlncRNAs in 424 patients with HCC were retrieved from The Cancer Genome Atlas database. Lasso and Cox regression analyses were performed to identify differentially expressed lncRNAs related to senescence. The prediction efficiency of the signature was checked using a receiver operating characteristic (ROC) curve, Kaplan–Meier analysis, Cox regression analyses, nomogram, and calibration. The risk groups of the gene set enrichment analysis, immune analysis, and prediction of the half-maximal inhibitory concentration (IC50) were also analyzed. Quantitative real-time polymerase chain reaction (qPCR) was used to confirm the levels of AC026412.3, AL451069.3, and AL031985.3 in normal hepatic and HCC cell lines.Results: We identified 3 srlncRNAs (AC026412.3, AL451069.3, and AL031985.3) and constructed a new risk model. The results of the ROC curve and Kaplan–Meier analysis suggested that it was concordant with the prediction. Furthermore, a nomogram model was constructed to accurately predict patient prognosis. The risk score also correlated with immune cell infiltration status, immune checkpoint expression, and chemosensitivity. The results of qPCR revealed that AC026412.3 and AL451069.3 were significantly upregulated in hepatoma cell lines.Conclusion: The novel srlncRNA (AC026412.3, AL451069.3, and AL031985.3) signatures may provide insights into new therapies and prognosis predictions for patients with HCC.

A novel disulfidptosis-related lncRNA signature for predicting prognosis and potential targeted therapy in hepatocellular carcinoma

“…AC026412.3 is differentially expressed between HCC and normal tissues and has been linked to poor prognosis of HCC patients. [43,44] There has not yet been any research on AL445309.1, AL132639.2, AC116049.1, and AC009486.2; however, our study might assist in understanding the potential functions of these 4 lncRNAs.…”

Comprehensive analysis of cuproptosis-related lncRNAs in immune infiltration and prognosis in hepatocellular carcinoma

“…We found that the four cuproptosis-related lncRNAs that were modeled were all up-regulated in the high-risk group. Through high-throughput bioinformatics analysis, many studies have shown that AL031985.3 is associated with the prognosis of HCC and can be used to build a predictive model for the prognosis of HCC [42][43][44]. Previous studies have found that SNHG18 is abnormally expressed in glioma tissue specimens, and high expression of SNHG18 in gliomas enhances their radiation resistance [45][46][47].…”

Constructed Risk Prognosis Model Associated with Disulfidptosis lncRNAs in HCC

“…Knockdown of this expression may inhibit the proliferation and migration ability of hepatocellular carcinoma cells by regulating miR-193b-5p, which, in turn, affects ubiquitin specific peptidase 10 (USP10) [18]. Compared with LO2, AC026412.3 was also highly expressed in a variety of hepatocellular carcinoma cells (Hepg2, Huh7, and Hep3B), which may be associated with poor prognosis in hepatocellular carcinoma patients [19]. Elevated MKLN1-AS has been demonstrated to be one of the causes of poor prognosis in hepatocellular carcinoma patients, which is also consistent with our findings [20].…”