Prognostic stratification based on m5C regulators acts as a novel biomarker for immunotherapy in hepatocellular carcinoma

Abstract

BackgroundImmunotherapy is a promising anti-cancer strategy in hepatocellular carcinoma (HCC). However, a limited number of patients can benefit from it. There are currently no reliable biomarkers available to find the potential beneficiaries. Methylcytosine (m5C) is crucial in HCC, but its role in forecasting clinical responses to immunotherapy has not been fully clarified.MethodsIn this study, we analyzed 371 HCC patients from The Cancer Genome Atlas (TCGA) database and investigated the expression of 18 m5C regulators. We selected 6 differentially expressed genes (DEGs) to construct a prognostic risk model as well as 2 m5C-related diagnostic models.ResultsThe 1-, 3-, and 5-year area under the curve (AUC) of m5C scores for the overall survival (OS) was 0.781/0.762/0.711, indicating the m5C score system had an ideal distinction of prognostic prediction for HCC. The survival analysis showed that patients with high-risk scores present a worse prognosis than the patients with low-risk scores (p< 0.0001). We got consistent results in 6 public cohorts and validated them in Xiangya real-world cohort by quantitative real-time PCR and immunohistochemical (IHC) assays. The high-m5C score group was predicted to be in an immune evasion state and showed low sensitivity to immunotherapy, but high sensitivity to chemotherapy and potential targeted drugs and agents, such as sepantronium bromide (YM-155), axitinib, vinblastine and docetaxel. Meanwhile, we also constructed two diagnostic models to distinguish HCC tumors from normal liver tissues or liver cirrhosis.ConclusionIn conclusion, our study helps to early screen HCC patients and select patients who can benefit from immunotherapy. Step forwardly, for the less likely beneficiaries, this study provides them with new potential targeted drugs and agents for choice to improve their prognosis.

RNA 5-methylcytosine writer NSUN5 promotes hepatocellular carcinoma cell proliferation via a ZBED3-dependent mechanism

“…Aberrant m 5 C modifications of RNA have been reported to be closely associated with tumorigenesis and immune infiltration across various cancer types, rendering them promising targets for anticancer therapy. Recently, prognostic models based on m 5 C-associated genes have emerged for HCC, offering novel insights into the role of this RNA modification in cancer development [ 22 – 26 ]. A previous study revealed that elevated NSUN5 expression promotes both in vitro HCC cell proliferation and migration as well as in vivo HCC tumor growth.…”

A pan-cancer analysis of the oncogenic and immunological roles of transglutaminase 1 (TGM1) in human cancer

“…Previous studies have partially explored the prognostic significance of m6A modification in BRCA and CHOL (Feng et al 2022c ; Wei et al 2023 ). Furthermore, m5C can serve as a potential biomarker for predicting the efficacy of LIHC immunotherapy (Liu et al 2022 ).…”