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丝裂原活化蛋白激酶激酶激酶在乙型肝炎病毒相关性肝细胞癌中的临床意义及作用机制探讨。

Clinical significance of mitogen-activated protein kinase kinase kinases in hepatitis B virus -related hepatocellular carcinoma and underlying mechanism exploration.

机构信息

Department of Burn and Plastic Surgery, Yancheng No. 1 People's Hospital, Yancheng, P. R. China.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, P. R. China.

出版信息

Bioengineered. 2022 Mar;13(3):6819-6838. doi: 10.1080/21655979.2022.2037224.

Abstract

The purpose of this research was to explore the diagnostic/prognostic significance and prospective molecular mechanisms of mitogen-activated protein kinase kinase kinases () in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Diagnostic/prognostic significance of was screened in the GSE1450 data set and validated in the Guangxi cohort. Various bioinformatics tools were used to explore the biological functions of prognosis-related genes. Subsequently, molecular biology assays were used to verify the biological functions and molecular mechanisms of specific gene. was observed to be differentially expressed in HCC and adjacent tissues with satisfactory diagnostic value. It was discovered in survival analysis that and were associated with overall survival (OS) of patients with HBV-related HCC in the GSE1450 data set and the Guangxi cohort. Nomograms were established based on prognosis-related genes and clinical factors for individualized risk assessment. The assays on HCC cells demonstrated that MAP3K13 regulated the death and proliferation of HCC cells by activating the JNK pathway and inducing the expression of apoptosis-related factors. In conclusion, our results suggested that might serve as a diagnostic biomarker in HBV-related HCC and and might serve as useful prognostic biomarkers. Besides, cytological assays prompted that MAP3K13 might impact the prognosis of HCC by regulating the JNK pathway and inducing apoptosis.

摘要

本研究旨在探讨丝裂原活化蛋白激酶激酶激酶 () 在乙型肝炎病毒 (HBV) 相关肝细胞癌 (HCC)中的诊断/预后意义和潜在的分子机制。在 GSE1450 数据集和广西队列中筛选了 的诊断/预后意义。使用各种生物信息学工具来探讨与预后相关基因的生物学功能。随后,通过分子生物学实验验证特定基因的生物学功能和分子机制。结果显示,在 HCC 及相邻组织中, 表达差异显著,具有良好的诊断价值。在 GSE1450 数据集和广西队列的生存分析中发现, 和 与 HBV 相关 HCC 患者的总生存期 (OS) 相关。基于预后相关基因和临床因素建立了列线图,用于个体化风险评估。对 HCC 细胞的实验表明,MAP3K13 通过激活 JNK 通路和诱导凋亡相关因子的表达来调节 HCC 细胞的死亡和增殖。总之,我们的研究结果表明, 可能是 HBV 相关 HCC 的诊断生物标志物, 和 可能是有用的预后生物标志物。此外,细胞学实验表明,MAP3K13 可能通过调节 JNK 通路和诱导细胞凋亡来影响 HCC 的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1fa/9278978/24a20cecc6d1/KBIE_A_2037224_UF0001_OC.jpg

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