Role of m &lt;sup&gt;5&lt;/sup&gt;C-Related Regulators in Diagnosis and Prediction of Prognosis in Hepatocellular Carcinoma

He, Yuting; Li, Jie; Zhang, Qiyao; Dang, Qin; Zheng, Qingyuan; Guo, Wenzhi

doi:10.2139/ssrn.3453320

Cited by 62 publications

(94 citation statements)

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“…To the best of our knowledge, this is the first study to identify 5mC-associated molecular subtypes in HCC. In contrast to a previously published study (He et al, 2020), our research revealed the underlying association between 5mC methylation and immunotherapy in HCC. Moreover, a greater number of 5mC regulators included and the comprehensive methodology used in our research enabled the identification of a reliable score.…”

Section: Discussioncontrasting

confidence: 99%

Novel Molecular Subtypes Associated With 5mC Methylation and Their Role in Hepatocellular Carcinoma Immunotherapy

Cao

Luo

et al. 2020

Front. Mol. Biosci.

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Background: 5-methylcytosine (5mC) has been reported in the prognosis of a variety of cancers, however, its role in hepatocellular carcinoma (HCC) has not been investigated yet. This study aimed at identifying the molecular subtypes associated with 5mC and establishing a relevant score to predict its prognosis in HCC. Methods: Somatic gene mutation data and gene expression data were retrieved from The Cancer Genome Atlas database. Molecular subtypes were identified by unsupervised clustering based on the expression of 5mC regulators, and the molecular features of each subtype were investigated by survival, mutation, gene set variation, and immune cell infiltration analyses. Next, we performed a differentially expressed analysis based on the new subtypes and selected the overlapping genes for further analysis. We undertook univariate Cox analysis to analyze these genes and constructed a prognostic model by lasso regression analysis. Meanwhile, survival and gene set enrichment analyses were used to explore the prognosis and the relevant pathways, respectively. The LIRI cohort from the International Cancer Genome Consortium database was used as a reference to validate the 5mC subtypes and 5mC score. Results: Twenty-one types of 5mC regulators were employed in this study, and three 5mC-associated molecular subtypes were identified. These three subtypes presented significant differences in prognosis, immune cell infiltration, immune checkpoint inhibitors, signaling pathways, and mutational features. Compared with cluster 3, cluster 2 exhibited significantly increased expression of PD-L1, TIM3, Galectin9, CTLA4, and CD80, while PD-L1, TIM3, and CD80 were higher in cluster 2 than in cluster 1. Furthermore, a 5mC-related score, composed of seven genes (SGPP2, SALL4, B3GNT7, ROR1, MYBL2, SLC7A1, and CAND2), was proven to be significantly associated with prognosis. The established subtypes and scores were thus successfully verified by the validated cohort.

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Section: Discussioncontrasting

confidence: 99%

Novel Molecular Subtypes Associated With 5mC Methylation and Their Role in Hepatocellular Carcinoma Immunotherapy

Cao

Luo

et al. 2020

Front. Mol. Biosci.

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“…RCMTs, which include NOL1/NOP2/sun (NSUN) subgroups of methyltransferases and DNA methyltransferase homologue DNMT2, are recognized as writers for catalyzing cytosine-5 methylation [37]. Additionally, RNA m 5 C binding proteins (readers), such as ALYREF and YBX1, exert biological effects by recognizing and binding to m 5 C sites [24]. The eraser protein demethylases, including enzymes of the TET family, exhibit reversible effects by mediating written RNA degradation.…”

Section: Rna M 5 C Regulatory Mechanismsmentioning

confidence: 99%

“…By interacting with the mitochondrial regulatory factor MTERF4, NSUN4 is recruited to the large subunit of the mitochondrial ribosome, thus facilitating mitochondrial ribosome assembly by modifying 12S rRNA methylation at position C911 [54]. Notably, NSUN4 is now considered an essential m 5 C regulator that is highly involved in HCC progression [24]. Another rRNA-specific RCMT is NSUN5 (also called Rcm1 in yeast), which is localized to nucleoli, and the methylation substrate of NSUN5 is at C2278 within the conserved domain IV of 25S rRNA [55].…”

Section: Writersmentioning

confidence: 99%

“…As one of the most common malignances worldwide, HCC remains poorly understood in terms of its pathogenesis and development. Recently, the regulatory role of RNA m 5 C on HCC progression has been uncovered, and evidence has indicated that the elevated m 5 C regulators NSUN4 and ALYREF are negatively correlated with poor survival outcome in HCC patients and exhibit great value as significant diagnostic and prognostic biomarkers for HCC [24]. Using 6 pairs of HCC tissues and adjacent nontumor tissues, the same study group demonstrated that the number of mRNA m 5 C peaks in HCC tissues was significantly higher than that in adjacent tissues, with a more widespread distribution [81].…”

Section: Hepatocellular Carcinoma (Hcc)mentioning

confidence: 99%

“…The alteration of m 5 C modification as well as its regulators has been proven to influence RNA stability, gene expression, and protein synthesis and thus has a great impact on various cellular and physical processes [15,[17][18][19][20][21][22]. Additionally, to date, RNA m 5 C modification and its regulators have been confirmed to play crucial roles in the pathogenesis of bladder cancer [23], hepatocellular carcinoma (HCC) [24], glioblastoma multiforme (GBM) [14] and leukemia [18], indicating the promising prospect of m 5 C modification in cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

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Advances in RNA cytosine-5 methylation: detection, regulatory mechanisms, biological functions and links to cancer

Xue

Zhao

2020

Biomark Res

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As an important posttranscriptional modification of RNA, 5-methylcytosine (m5C) has attracted increasing interest recently, with accumulating evidence suggesting the involvement of RNA m5C modification in multiple cellular processes as well as tumorigenesis. Cooperatively, advances in m5C detection techniques have enabled transcriptome mapping of RNA methylation at single-nucleotide resolution, thus stimulating m5C-based investigations. In this review, we summarize currently available approaches for detecting m5C distribution in RNA as well as the advantages and disadvantages of these techniques. Moreover, we elucidate the regulatory mechanisms of RNA m5C modification by introducing the molecular structure, catalytic substrates, cellular distributions and biological functions of RNA m5C regulators. The functional consequences of m5C modification on mRNAs, tRNAs, rRNAs and other RNA species, including viral RNAs and vault RNAs, are also discussed. Finally, we review the role of RNA m5C modification in cancer pathogenesis and progression, in hopes of providing new insights into cancer treatment.

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Genetic variants in RNA m⁵C modification genes associated with survival and chemotherapy efficacy of colorectal cancer

et al. 2022

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Background Colorectal cancer is one of the most common malignant digestive tract tumors with a poor prognosis. RNA 5‐methylcytosine (m5C) is an important posttranscriptional widespread modification involved in many biological processes. However, the association between genetic variations of m5C modification genes and the prognostic value of colorectal cancer remains unclear. Methods We investigated the association between candidate single nucleotide polymorphisms (SNPs) in 13 m5C modification genes and colorectal cancer overall survival (OS) after chemotherapy by the Cox regression model. The combined effect of selected SNPs on OS, progression‐free survival (PFS), and disease control rate (DCR) was assessed by the number of risk alleles (NRA). The GTEx and TCGA database were used to perform expression qualitative trait locus (eQTL) analysis. Results We identified that two SNPs in YBX1 were associated with OS after chemotherapy (HR = 1.43, p = 0.001 for rs10890208; HR = 1.36, p = 0.025 for rs3862218). A striking dose–response effect between NRA and OS after chemotherapy was found (ptrend = 0.002). The DCR of patients receiving oxaliplatin chemotherapy in the 3–4 NRA group was markedly reduced in comparison to that in the 0–2 NRA group (OR = 1.49, p = 0.036). Moreover, YBX1 mRNA expression was significantly overexpressed in tumor tissues (p < 0.05) in the TCGA database, and eQTL analysis demonstrated that the two SNPs were associated with YBX1 (p = 0.003 for rs10890208 and p = 0.024 for rs3862218). Conclusion Our study indicates that genetic variants in m5C modification genes may mediate changes in YBX1 mRNA levels and affect the chemotherapeutic efficacy of colorectal cancer patients.

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Role of m <sup>5</sup>C-Related Regulators in Diagnosis and Prediction of Prognosis in Hepatocellular Carcinoma

Cited by 62 publications

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Novel Molecular Subtypes Associated With 5mC Methylation and Their Role in Hepatocellular Carcinoma Immunotherapy

Novel Molecular Subtypes Associated With 5mC Methylation and Their Role in Hepatocellular Carcinoma Immunotherapy

Advances in RNA cytosine-5 methylation: detection, regulatory mechanisms, biological functions and links to cancer

Genetic variants in RNA m⁵C modification genes associated with survival and chemotherapy efficacy of colorectal cancer

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Role of m <sup>5</sup>C-Related Regulators in Diagnosis and Prediction of Prognosis in Hepatocellular Carcinoma

Cited by 62 publications

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Novel Molecular Subtypes Associated With 5mC Methylation and Their Role in Hepatocellular Carcinoma Immunotherapy

Novel Molecular Subtypes Associated With 5mC Methylation and Their Role in Hepatocellular Carcinoma Immunotherapy

Advances in RNA cytosine-5 methylation: detection, regulatory mechanisms, biological functions and links to cancer

Genetic variants in RNA m5C modification genes associated with survival and chemotherapy efficacy of colorectal cancer

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Genetic variants in RNA m⁵C modification genes associated with survival and chemotherapy efficacy of colorectal cancer