Construction of a Necroptosis-Related miRNA Signature for Predicting the Prognosis of Patients With Hepatocellular Carcinoma

Abstract

Background: Many miRNAs have been demonstrated to be associated with the prognosis of hepatocellular carcinoma (HCC). However, how to combine necroptosis-related miRNAs to achieve the best predictive effect in estimating HCC patient survival has not been explored.Methods: The mRNA and miRNA expression profile were downloaded from a public database (TCGA-LIHC cohort). Necroptosis-related genes were obtained from previous references, and necroptosis-related miRNAs were identified using Pearson analysis. Subsequently, differential expression miRNAs (DEms) were identified in HCC and paracancer normal samples based on necroptosis-related miRNA expression. The whole set with HCC was randomized into a training set and testing set (1:1). LASSO-Cox regression analysis was used to construct an miRNA signature. Multiple statistical methods were used to validate the clinical benefit of signature in HCC patients, including receiver operator characteristic (ROC) curves, Kaplan–Meier survival analyses, and decision curve analysis (DCA). The downstream target genes of miRNAs were obtained from different online tools, and the potential pathways involved in miRNAs were explored. Finally, we conducted RT-qPCR in SK-HEP-1, THLE-3, and HUH-7 cell lines for miRNAs involved in the signature.Results: The results showed that a total of eight specific necroptosis-related miRNAs were screened between HCC and adjacent tissues in the training set. Subsequently, based on the aforementioned miRNAs, 5-miRNA signature (miR-139-5p, hsa-miR-326, miR-10b-5p, miR-500a-3p, and miR-592) was generated by LASSO-Cox regression analysis. Multivariate Cox regression analysis showed that the risk scores were independent prognostic indicators in each set. The area under curves (AUCs) of 1 year, 3 years, 5 years, and 7 years were high in each set (AUC >0.7). DCA analysis also revealed that the risk score had a potential benefit than other clinical characteristics. Meanwhile, survival analysis showed that the high-risk group showed low survival probabilities. Moreover, the results of enrichment analysis showed that specific miRNAs were mainly enriched in the cAMP signaling pathway and TNF signaling pathway. Finally, the results of RT-qPCR were consistent with the prediction results in public databases.Conclusion: Our study establishes a robust tool based on 5-necroptosis-related miRNAs for the prognostic management of HCC patients.

Qualification of Necroptosis-Related lncRNA to Forecast the Treatment Outcome, Immune Response, and Therapeutic Effect of Kidney Renal Clear Cell Carcinoma

“…The function of lncRNAs in sequestering and inactivating one or more miRNA species was studied also in the necroptosis response in HCC [42]. In breast cancer, Xu et al, Chen et al, Xie et al, and Zhang et al studied the link between tumor microenvironment and NLR signatures [43][44][45][46], as well as miRNA signatures [47]. An axis linking an lncRNA with a microRNA and the target gene was shown in bladder cancer progression and metastasis [48,49].…”

Identification and Characterization of an Ageing-Associated 13-lncRNA Signature That Predicts Prognosis and Immunotherapy in Hepatocellular Carcinoma

“…Based on previous publications, 5 prognostic risk models were selected, including 8-gene [18], 8-gene [19], 10-gene [20], 2-gene [21], and 5-gene signatures [22], and compared these signatures with our model. Te rms package in R was employed to calculate the concordance index (C-index) of the various signatures and to compare the prediction performance of these models in HCC samples.…”

miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma

“…Among them, miR-326, miR-30d-5p, let-7c-5p, miR-5003-3p, miR-760, and miR-7-5p constitute prognostic biomarkers of immune infiltration [ 10 ]. Others like miR-139-5p, hsa-miR-326, miR-10b-5p, miR-500a-3p, and miR-592 are representative of necroptosis [ 11 ]. Even though these studies provide great knowledge, validation experiments are needed in external patient cohorts [ 10 , 11 , 12 , 13 ].…”

“…Others like miR-139-5p, hsa-miR-326, miR-10b-5p, miR-500a-3p, and miR-592 are representative of necroptosis [ 11 ]. Even though these studies provide great knowledge, validation experiments are needed in external patient cohorts [ 10 , 11 , 12 , 13 ]. Using a different approach, many other studies have tried to elucidate mechanistic pathways based on the regulation of miRNAs by competing endogenous RNAs such as long-non coding RNAs (lncRNAs) [ 14 ] or circular RNAs (circRNAs) [ 15 ].…”