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Identification and Validation of a Prognostic Prediction Model of m6A Regulator-Related LncRNAs in Hepatocellular Carcinoma

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单位: [1]Wenzhou Med Univ, Sch Publ Hlth & Management, Dept Epidmiol & Biostat, Wenzhou, Peoples R China [2]Huazhong Univ Sci & Technol, Tongji Hosp, Dept Oncol, Wuhan, Peoples R China [3]Wenzhou Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Wenzhou, Peoples R China [4]Wenzhou Med Univ, Key Lab Diag & Treatment Severe Hepatopancreat Di, Affiliated Hosp 1, Wenzhou, Peoples R China
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关键词: hepatocellular carcinoma m6A regulators long non-coding RNA prognosis prediction therapy

摘要:
Hepatocellular carcinoma (HCC) is a highly invasive malignancy prone to recurrence, and patients with HCC have a low 5-year survival rate. Long non-coding RNAs (lncRNAs) play a vital role in the occurrence and development of HCC. N6-methyladenosine methylation (m6A) is the most common modification influencing cancer development. Here, we used the transcriptome of m6A regulators and lncRNAs, along with the complete corresponding clinical HCC patient information obtained from The Cancer Genome Atlas (TCGA), to explore the role of m6A regulator-related lncRNA (m6ARlnc) as a prognostic biomarker in patients with HCC. The prognostic m6ARlnc was selected using Pearson correlation and univariate Cox regression analyses. Moreover, three clusters were obtained via consensus clustering analysis and further investigated for differences in immune infiltration, immune microenvironment, and prognosis. Subsequently, nine m6ARlncs were identified with Lasso-Cox regression analysis to construct the prognostic signature m6A-9LPS for patients with HCC in the training cohort (n = 226). Based on m6A-9LPS, the risk score for each case was calculated. Patients were then divided into high- and low-risk subgroups based on the cutoff value set by the X-tile software. m6A-9LPS showed a strong prognosis prediction ability in the validation cohort (n = 116), the whole cohort (n = 342), and even clinicopathological stratified survival analysis. Combining the risk score and clinical characteristics, we established a nomogram for predicting the overall survival (OS) of patients. To further understand the mechanism underlying the m6A-9LPS-based classification of prognosis differences, KEGG and GO enrichment analyses, competitive endogenous RNA (ceRNA) network, chemotherapeutic agent sensibility, and immune checkpoint expression level were assessed. Taken together, m6A-9LPS could be used as a precise prediction model for the prognosis of patients with HCC, which will help in individualized treatment of HCC.

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出版当年[2020]版:
大类 | 2 区 生物
小类 | 3 区 生化与分子生物学
最新[2025]版:
大类 | 3 区 生物学
小类 | 3 区 生化与分子生物学
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出版当年[2019]版:
Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版:
Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

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第一作者单位: [1]Wenzhou Med Univ, Sch Publ Hlth & Management, Dept Epidmiol & Biostat, Wenzhou, Peoples R China
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通讯机构: [3]Wenzhou Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Wenzhou, Peoples R China [4]Wenzhou Med Univ, Key Lab Diag & Treatment Severe Hepatopancreat Di, Affiliated Hosp 1, Wenzhou, Peoples R China
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