An m6A-Related lncRNA Signature Predicts the Prognosis of Hepatocellular Carcinoma

Objective: The purpose of this study was to establish an N6-methylandenosine (m6A)-related long non-coding RNA (lncRNA) signature to predict the prognosis of hepatocellular carcinoma (HCC). Methods: Pearson correlation analysis was used to identify m6A-related lncRNAs. We then performed univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis to construct an m6A-related lncRNA signature. Based on the cutoff value of the risk score determined by the X-title software, we divided the HCC patients into high -and low-risk groups. A time-dependent ROC curve was used to evaluate the predictive value of the model. Finally, we constructed a nomogram based on the m6A-related lncRNA signature. Results: ZEB1-AS1, MIR210HG, BACE1-AS, and SNHG3 were identified to comprise an m6A-related lncRNA signature. These four lncRNAs were upregulated in HCC tissues compared to normal tissues. The prognosis of patients with HCC in the low-risk group was significantly longer than that in the high-risk group. The M6A-related lncRNA signature was significantly associated with clinicopathological features and was established as a risk factor for the prognosis of patients with HCC. The nomogram based on the m6A-related lncRNA signature had a good distinguishing ability and consistency. Conclusion: We identified an m6A-related lncRNA signature and constructed a nomogram model to evaluate the prognosis of patients with HCC.

[1]  Zhongxin Li,et al.  Comprehensive analysis of N6-methylandenosine regulators and m6A-related RNAs as prognosis factors in colorectal cancer , 2021, Molecular therapy. Nucleic acids.

[2]  Y. Zhang,et al.  Identification and Validation of Ferroptosis-Related LncRNA Signatures as a Novel Prognostic Model for Colon Cancer , 2022, Frontiers in Immunology.

[3]  Lin-Na Tan,et al.  Identifying a Hypoxia-Related Long Non-Coding RNAs Signature to Improve the Prediction of Prognosis and Immunotherapy Response in Hepatocellular Carcinoma , 2021, Frontiers in Genetics.

[4]  Kefei Yuan,et al.  IL‐6–induced cGGNBP2 encodes a protein to promote cell growth and metastasis in intrahepatic cholangiocarcinoma , 2021, Hepatology.

[5]  M. Zhang,et al.  Development and Validation of an Autophagy-Related Gene Signature for Predicting the Prognosis of Hepatocellular Carcinoma , 2021, BioMed research international.

[6]  C. Neuzillet,et al.  Biomarkers in Hepatobiliary Cancers: What Is Useful in Clinical Practice? , 2021, Cancers.

[7]  Maolan Li,et al.  A ten N6‐methyladenosine‐related long non‐coding RNAs signature predicts prognosis of triple‐negative breast cancer , 2021, Journal of clinical laboratory analysis.

[8]  Hong-Yuan Li,et al.  Identification of autophagy‐related long non‐coding RNA prognostic signature for breast cancer , 2021, Journal of cellular and molecular medicine.

[9]  Xutong Li,et al.  Prognostic significance of inflammation-based score in patients with hepatocellular carcinoma after liver transplantation , 2021, European journal of gastroenterology & hepatology.

[10]  Jian Zhang,et al.  Prognostic value of inflammation-based indices in patients with resected hepatocellular carcinoma , 2020, BMC Cancer.

[11]  Yao Lin,et al.  Identification of Epithelial–Mesenchymal Transition-Related lncRNA With Prognosis and Molecular Subtypes in Clear Cell Renal Cell Carcinoma , 2020, Frontiers in Oncology.

[12]  W. Xie,et al.  ALKBH1 Promotes Lung Cancer by Regulating m6A RNA Demethylation. , 2020, Biochemical pharmacology.

[13]  C. Qin,et al.  Four Autophagy-Related lncRNAs Predict the Prognosis of HCC through Coexpression and ceRNA Mechanism , 2020, BioMed research international.

[14]  M. Taheri,et al.  The Role of Long Non-coding RNAs in Cancer Metabolism: A Concise Review , 2020, Frontiers in Oncology.

[15]  Lei Zheng,et al.  Gene Signatures and Prognostic Values of m6A Regulators in Hepatocellular Carcinoma , 2020, Frontiers in Genetics.

[16]  X. Zou,et al.  m6A Reader HNRNPA2B1 Promotes Esophageal Cancer Progression via Up-Regulation of ACLY and ACC1 , 2020, Frontiers in Oncology.

[17]  Yanhong Cheng,et al.  Development and Validation of an Immune-Related lncRNA Signature for Predicting the Prognosis of Hepatocellular Carcinoma , 2020, Frontiers in Genetics.

[18]  Xutong Li,et al.  Development and validation of a m6A-related gene signature for predicting the prognosis of hepatocellular carcinoma. , 2020, Biomarkers in medicine.

[19]  Peng Liu,et al.  METTL3 regulates m6A in endometrioid epithelial ovarian cancer independently of METTl14 and WTAP , 2020, Cell biology international.

[20]  Hongda Pan,et al.  Development and Validation of an m6A RNA Methylation Regulator-Based Signature for Prognostic Prediction in Cervical Squamous Cell Carcinoma , 2020, Frontiers in Oncology.

[21]  Yongyan Wu,et al.  Crosstalk between RNA m6A Modification and Non-coding RNA Contributes to Cancer Growth and Progression , 2020, Molecular therapy. Nucleic acids.

[22]  Xiaoyu Chen,et al.  Novel insights into the interplay between m6A modification and noncoding RNAs in cancer , 2020, Molecular Cancer.

[23]  J. Priyadharsini,et al.  The m6A readers YTHDF1 and YTHDF3 aberrations associated with metastasis and predict poor prognosis in breast cancer patients. , 2020, American journal of cancer research.

[24]  K. Huang,et al.  N6-Methylandenosine-Related lncRNAs Are Potential Biomarkers for Predicting the Overall Survival of Lower-Grade Glioma Patients , 2020, Frontiers in Cell and Developmental Biology.

[25]  Li Liu,et al.  Long noncoding RNA UPK1A-AS1 indicates poor prognosis of hepatocellular carcinoma and promotes cell proliferation through interaction with EZH2 , 2020, Journal of experimental & clinical cancer research : CR.

[26]  Qiuju Yang,et al.  LncRNA MIR210HG Facilitates Non-Small Cell Lung Cancer Progression Through Directly Regulation of miR-874/STAT3 Axis , 2020, Dose-response : a publication of International Hormesis Society.

[27]  Yao Wang,et al.  LncZEB1-AS1 regulates hepatocellular carcinoma bone metastasis via regulation of the miR-302b-EGFR-PI3K-AKT axis , 2020, Journal of Cancer.

[28]  Peihong Wu,et al.  Identification and Validation of a Prognostic lncRNA Signature for Hepatocellular Carcinoma , 2020, Frontiers in Oncology.

[29]  J. Lang,et al.  FTO demethylates m6A modifications in HOXB13 mRNA and promotes endometrial cancer metastasis by activating the WNT signalling pathway , 2020, RNA biology.

[30]  Y. Shu,et al.  Interaction between N6-methyladenosine (m6A) modification and noncoding RNAs in cancer , 2020, Molecular Cancer.

[31]  Wenjun Yang,et al.  The Prediction of Survival in Hepatocellular Carcinoma Based on A Four Long Non-coding RNAs Expression Signature , 2020, Journal of Cancer.

[32]  Ruifang Wang,et al.  MIR210HG promotes cell proliferation and invasion by regulating miR-503-5p/TRAF4 axis in cervical cancer , 2020, Aging.

[33]  Yang Wang,et al.  ALKBH5-mediated m6A demethylation of lncRNA PVT1 plays an oncogenic role in osteosarcoma , 2020, Cancer Cell International.

[34]  Honghai Xu,et al.  The Prognostic Role of a Combined Fibrinogen and Neutrophil-to-Lymphocyte Ratio Score in Patients with Resectable Hepatocellular Carcinoma: A Retrospective Study , 2020, Medical science monitor : international medical journal of experimental and clinical research.

[35]  Qi Zhou,et al.  The m6A eraser FTO facilitates proliferation and migration of human cervical cancer cells , 2019, Cancer Cell International.

[36]  Qi Zhou,et al.  The m6A eraser FTO facilitates proliferation and migration of human cervical cancer cells , 2019, Cancer Cell International.

[37]  Jian Wu,et al.  LncSNHG3/miR-139-5p/BMI1 axis regulates proliferation, migration, and invasion in hepatocellular carcinoma , 2019, OncoTargets and therapy.

[38]  Yuan-yuan Zhang,et al.  The long noncoding RNA MIR210HG promotes tumor metastasis by acting as a ceRNA of miR-1226-3p to regulate mucin-1c expression in invasive breast cancer , 2019, Aging.

[39]  A. Fatica,et al.  Interplay Between N6-Methyladenosine (m6A) and Non-coding RNAs in Cell Development and Cancer , 2019, Front. Cell Dev. Biol..

[40]  Weijia Li,et al.  MIR210HG predicts poor prognosis and functions as an oncogenic lncRNA in hepatocellular carcinoma. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[41]  M. Taheri,et al.  β-Secretase 1 and its Naturally Occurring Anti-Sense RNA are Down-Regulated in Gastric Cancer , 2019, Pathology & Oncology Research.

[42]  A. Ke,et al.  LncRNA SNHG3 induces EMT and sorafenib resistance by modulating the miR‐128/CD151 pathway in hepatocellular carcinoma , 2018, Journal of cellular physiology.

[43]  A. Jemal,et al.  Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries , 2018, CA: a cancer journal for clinicians.

[44]  Xiao-Qing Wang,et al.  Long Noncoding RNA miR210HG Sponges miR-503 to Facilitate Osteosarcoma Cell Invasion and Metastasis. , 2017, DNA and cell biology.

[45]  M. Kudo,et al.  Asia–Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update , 2017, Hepatology International.

[46]  D. Glavač,et al.  Long Noncoding RNAs as Biomarkers in Cancer , 2017, Disease markers.

[47]  Ze-Guang Han,et al.  A three-lncRNA signature derived from the Atlas of ncRNA in cancer (TANRIC) database predicts the survival of patients with head and neck squamous cell carcinoma. , 2017, Oral oncology.

[48]  Chao Chen,et al.  Long Noncoding RNA miR210HG as a Potential Biomarker for the Diagnosis of Glioma , 2016, PloS one.

[49]  Suwei Wang,et al.  Long non-coding RNA BACE1-AS is a novel target for anisomycin-mediated suppression of ovarian cancer stem cell proliferation and invasion. , 2016, Oncology reports.

[50]  Suwei Wang,et al.  Long non-coding RNA BACE 1-AS is a novel target for anisomycin-mediated suppression of ovarian cancer stem cell proliferation and invasion , 2016 .

[51]  H. Li,et al.  Upregulation of long noncoding RNA ZEB1-AS1 promotes tumor metastasis and predicts poor prognosis in hepatocellular carcinoma , 2015, Oncogene.

[52]  鄒佩玲,et al.  美國癌症基因體圖譜計畫TCGA(The Cancer Genome Atlas)簡介 , 2013 .

[53]  A. Smilde,et al.  Double-check: validation of diagnostic statistics for PLS-DA models in metabolomics studies , 2011, Metabolomics.

[54]  T. Morgan,et al.  Expression of a noncoding RNA is elevated in Alzheimer's disease and drives rapid feed-forward regulation of β-secretase , 2008, Nature Medicine.

[55]  D. Rimm,et al.  X-Tile , 2004, Clinical Cancer Research.

[56]  Wei-Hao Wang,et al.  Studies , 1926 .