The Prognostic Value and Immune Landscapes of a m6A/m5C/m1A-Related LncRNAs Signature in Head and Neck Squamous Cell Carcinoma

Wang, Enhao; Yang, Li; Ming, Ruijie; Wei, Jiahui; Du, Peiyu; Zhou, Peng; Zong, Shimin; Xiao, Hongjun

doi:10.3389/fcell.2021.718974

Cited by 43 publications

(49 citation statements)

References 88 publications

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“…Modification of m 6 A, m 5 C, m 1 A, and m 7 G are the common type of modification in RNA and plays critical roles in cancer development ( Teng et al, 2021 ; Xu F. et al, 2021 ; Xu R. et al, 2021 ). And RNA methylation highly interconnected with hypoxia, immune response and EMT( Lin et al, 2019 ; Chao et al, 2020 ; Wang E. et al, 2021 ). In previous study, researcher identified hypoxia can induced the sumolytion of m 6 A enzyme( Hou et al, 2021 ), hypoxia-inducible factor-1 alpha (HIF-1α) can drive m 5 C modification to promote tumorigenesis( Wang J.…”

Section: Discussionmentioning

confidence: 99%

A Prognostic Risk Score Based on Hypoxia-, Immunity-, and Epithelialto-Mesenchymal Transition-Related Genes for the Prognosis and Immunotherapy Response of Lung Adenocarcinoma

Ouyang

Jiang

et al. 2022

Front. Cell Dev. Biol.

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Background: Lung adenocarcinoma (LUAD), the most common subtype of non-small cell lung cancer (NSCLC), is associated with poor prognosis. However, current stage-based clinical methods are insufficient for survival prediction and decision-making. This study aimed to establish a novel model for evaluating the risk of LUAD based on hypoxia, immunity, and epithelial-mesenchymal transition (EMT) gene signatures.Methods: In this study, we used data from TCGA-LUAD for the training cohort and GSE68465 and GSE72094 for the validation cohorts. Immunotherapy datasets GSE135222, GSE126044, and IMvigor210 were obtained from a previous study. Using bioinformatic and machine algorithms, we established a risk model based on hypoxia, immune, and EMT gene signatures, which was then used to divide patients into the high and low risk groups. We analyzed differences in enriched pathways between the two groups, following which we investigated whether the risk score was correlated with stemness scores, genes related to m6A, m5C, m1A and m7G modification, the immune microenvironment, immunotherapy response, and multiple anti-cancer drug sensitivity.Results: Overall survival differed significantly between the high-risk and low-risk groups (HR = 4.26). The AUCs for predicting 1-, 3-, and 5-year survival were 0.763, 0.766, and 0.728, respectively. In the GSE68465 dataset, the HR was 2.03, while the AUCs for predicting 1-, 3-, and 5-year survival were 0.69, 0.651, and 0.618, respectively. The corresponding values in the GSE72094 dataset were an HR of 2.36 and AUCs of 0.653, 0.662, and 0.749, respectively. The risk score model could independently predict OS in patients with LUAD, and highly correlated with stemness scores and numerous m6A, m5C, m1A and m7G modification-related genes. Furthermore, the risk model was significantly correlated with multiple immune microenvironment characteristics. In the GSE135222 dataset, the HR was 4.26 and the AUC was 0.702. Evaluation of the GSE126044 and IMvigor210 cohorts indicated that PD-1/PD-LI inhibitor treatment may be indicated in patients with low risk scores, while anti-cancer therapy with various drugs may be indicated in patients with high risk scores.Conclusion: Our novel risk model developed based on hypoxia, immune, and EMT gene signatures can aid in predicting clinical prognosis and guiding treatment in patients with LUAD.

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Section: Discussionmentioning

confidence: 99%

A Prognostic Risk Score Based on Hypoxia-, Immunity-, and Epithelialto-Mesenchymal Transition-Related Genes for the Prognosis and Immunotherapy Response of Lung Adenocarcinoma

Ouyang

Jiang

et al. 2022

Front. Cell Dev. Biol.

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“…Huang et al constructed an m5C-associated lncRNA prognostic signature that accurately predicted breast cancer patient’s prognosis and immune microenvironment characteristics ( Huang et al, 2021 ). A recent study has identified the critical role of m6A/m5C/m1A-related lncRNA-based prognostic signature in predicting molecular subtypes and prognosis of head and neck tumors ( Wang et al, 2021a ). However, to the best of our knowledge, no prognostic signature based on m6A/m1A/m5C/m7G-related lncRNAs has been found to be accurate and applicable to CC patients.…”

Section: Discussionmentioning

confidence: 99%

Identification of RNA Methylation-Related lncRNAs Signature for Predicting Hot and Cold Tumors and Prognosis in Colon Cancer

Man

Huang

et al. 2022

Front. Genet.

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N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), and 7-methylguanosine (m7G) are the major forms of RNA methylation modifications, which are closely associated with the development of many tumors. However, the prognostic value of RNA methylation-related long non-coding RNAs (lncRNAs) in colon cancer (CC) has not been defined. This study summarised 50 m6A/m1A/m5C/m7G-related genes and downloaded 41 normal and 471 CC tumor samples with RNA-seq data and clinicopathological information from The Cancer Genome Atlas (TCGA) database. A total of 1057 RNA methylation-related lncRNAs (RMlncRNAs) were identified with Pearson correlation analysis. Twenty-three RMlncRNAs with prognostic values were screened using univariate Cox regression analysis. By consensus clustering analysis, CC patients were classified into two molecular subtypes (Cluster 1 and Cluster 2) with different clinical outcomes and immune microenvironmental infiltration characteristics. Cluster 2 was considered to be the “hot tumor” with a better prognosis, while cluster 1 was regarded as the “cold tumor” with a poorer prognosis. Subsequently, we constructed a seven-lncRNA prognostic signature using the least absolute shrinkage and selection operator (LASSO) Cox regression. In combination with other clinical traits, we found that the RNA methylation-related lncRNA prognostic signature (called the “RMlnc-score”) was an independent prognostic factor for patients with colon cancer. In addition, immune infiltration, immunotherapy response analysis, and half-maximum inhibitory concentration (IC50) showed that the low RMlnc-score group was more sensitive to immunotherapy, while the high RMlnc-score group was sensitive to more chemotherapeutic agents. In summary, the RMlnc-score we developed could be used to predict the prognosis, immunotherapy response, and drug sensitivity of CC patients, guiding more accurate, and personalized treatment regimens.

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“…In eukaryotic messenger RNA (mRNA) regulation, N 6methyladenosine (m6A), N 1 -methyladenosine (m1A), and 5methylcytosine (m5C) modifications exist. Several studies have confirmed that m6A, m1A, and m5C regulated genes play important roles in m6A, m1A, and m5C modifications (7)(8)(9)(10)(11). Recent research has found that m6A, m1A, and m5C regulated gene expression levels are associated with tumor progression (11)(12)(13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 91%

“…Currently, the roles of m6A, m1A, and m5C regulated genes in HCC progression are not yet fully understood. Therefore, in this study, data from The Cancer Genome Atlas (TCGA) database were used to elucidate the biological functions and network involved in m6A/m1A/m5C regulated genes ( 8 ), and the roles of m6A/m1A/m5C regulated genes in the prognosis of HCC patients were identified. The risk model and nomogram of m6A/m1A/m5C regulated genes were constructed to determine the prognosis of HCC patients.…”

Section: Introductionmentioning

confidence: 99%

The m6A/m5C/m1A Regulated Gene Signature Predicts the Prognosis and Correlates With the Immune Status of Hepatocellular Carcinoma

Zhang

et al. 2022

Front. Immunol.

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RNA modification of m6A/m5C/m1A contributes to the occurrence and development of cancer. Consequently, this study aimed to investigate the functions of m6A/m5C/m1A regulated genes in the prognosis and immune microenvironment of hepatocellular carcinoma (HCC). The expression levels of 45 m6A/m5C/m1A regulated genes in HCC tissues were determined. The functional mechanisms and protein–protein interaction network of m6A/m5C/m1A regulated genes were investigated. The Cancer Genome Atlas (TCGA) HCC gene set was categorized based on 45 m6A/m5C/m1A regulated genes, and survival analysis was used to determine the relationship between the overall survival of HCC patients in subgroups. Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were used to construct the risk model and nomogram for m6A/m5C/m1A regulated genes. The relationships between m6A/m5C/m1A regulated gene subsets and risk model and immune cell infiltration were analyzed using CIBERSORT. m6A/m5C/m1A regulated genes were involved in mRNA and RNA modifications, mRNA and RNA methylation, mRNA and RNA stability, and other processes. There was a statistically significant difference between cluster1 and cluster2 groups of genes regulated by m6A/m5C/m1A. The prognosis of cluster1 patients was significantly better than that of cluster2 patients. There were statistically significant differences between the two cluster groups in terms of fustat status, grade, clinical stage, and T stage of HCC patients. The risk model comprised the overexpression of YBX1, ZC3H13, YTHDF1, TRMT10C, YTHDF2, RRP8, TRMT6, LRPPRC, and IGF2BP3, which contributed to the poor prognosis of HCC patients. The high-risk score was associated with prognosis, fustat status, grade, clinical stage, T stage, and M stage and was an independent risk factor for poor prognosis in HCC patients. High-risk score mechanisms included spliceosome, RNA degradation, and DNA replication, among others, and high-risk was closely related to stromal score, CD4 memory resting T cells, M0 macrophages, M1 macrophages, resting mast cells, CD4 memory activated T cells, and follicular helper T cells. In conclusion, the cluster subgroup and risk model of m6A/m5C/m1A regulated genes were associated with the poor prognosis and immune microenvironment in HCC and are expected to be the new tools for assessing the prognosis of HCC patients.

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The Prognostic Value and Immune Landscapes of a m6A/m5C/m1A-Related LncRNAs Signature in Head and Neck Squamous Cell Carcinoma

Cited by 43 publications

References 88 publications

A Prognostic Risk Score Based on Hypoxia-, Immunity-, and Epithelialto-Mesenchymal Transition-Related Genes for the Prognosis and Immunotherapy Response of Lung Adenocarcinoma

A Prognostic Risk Score Based on Hypoxia-, Immunity-, and Epithelialto-Mesenchymal Transition-Related Genes for the Prognosis and Immunotherapy Response of Lung Adenocarcinoma

Identification of RNA Methylation-Related lncRNAs Signature for Predicting Hot and Cold Tumors and Prognosis in Colon Cancer

The m6A/m5C/m1A Regulated Gene Signature Predicts the Prognosis and Correlates With the Immune Status of Hepatocellular Carcinoma

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