Development and validation of a m6A-related gene signature for predicting the prognosis of hepatocellular carcinoma

2020 ◽  
Vol 14 (13) ◽  
pp. 1217-1228
Author(s):  
Weihao Kong ◽  
Xutong Li ◽  
Honghai Xu ◽  
Yufeng Gao
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Multivariate Regression Analysis ◽  
Gene Signature ◽  
Gene Expression Omnibus ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Risk Genes ◽  
Related Risk ◽  
Cancer Genome Atlas

Background: This study aimed to investigate the prognostic role of m6A methylation regulators in hepatocellular carcinoma (HCC). Materials & methods: Gene expression matrices were downloaded from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium, and Gene Expression Omnibus databases. Univariate and multivariate regression analysis were utilized to determine the m6A risk genes. Results: Two m6A-related risk genes (YTHDF1, YTHDF2) were identified in the TCGA HCC cohort. The m6A-correlated risk score is an independent risk factor for the overall survival of the TCGA HCC cohort. Finally, we verified the reliability of our results using three external datasets. Conclusion: The m6A-correlated gene signature has prognostic value in HCC patients and thus provides guidance for the treatment of HCC.

scholarly journals The role of miR-92b in cholangiocarcinoma patients

2018 ◽  
Vol 33 (3) ◽  
pp. 293-300 ◽  
Author(s):  
Min-hang Zhou ◽  
Hong-wei Zhou ◽  
Mo Liu ◽  
Jun-zhong Sun
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Gene Expression Omnibus ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Positive Regulation ◽  
Cancer Genome Atlas ◽  
High Level ◽  
Genome Atlas

Purpose: The role of microRNA (miRNA) in cholangiocarcinoma was not clear. The aim of this study was to find the potential diagnostic and prognostic miRNA in cholangiocarcinoma patients. Methods: The miRNA expression profiles in cholangiocarcinoma patients from The Cancer Genome Atlas and Gene Expression Omnibus (GSE53870) were analyzed. The comparison of overall survival was performed using the Kaplan–Meier method. The targeted genes of prognostic miRNA were identified in miRanda, PicTar, or TargetScan, and their cell signaling pathways were analyzed by the Database for Annotation, Visualization and Integrated Discovery. Results: In The Cancer Genome Atlas and the Gene Expression Omnibus miRNA dataset, miR-92b and miR-99a were found with concordant directionality, up-regulated and down-regulated, respectively. In The Cancer Genome Atlas survival data, patients with the high level of miR-99b had obviously shorter overall survival time ( P=0.038). However, the level of miR-99a was not found to be significant. The 17 shared target genes of miR-92b were identified, such as DAB21IP, BCL21L11, SPHK2, PER2, and TSC1. The related pathways included positive regulation of transcription, positive regulation of cellular biosynthetic process, regulation of programmed cell death, etc. Conclusion: miR-92b was up-regulated in cholangiocarcinoma compared with normal controls. The high level of miR-92b was associated with adverse outcomes in cholangiocarcinoma patients, which might be partly explained by the targeted genes of miR-92b and their signaling pathways.

Using machine learning method to identify MYLK as a novel marker to predict biochemical recurrence in prostate cancer

2021 ◽  
Vol 15 (1) ◽  
pp. 29-41
Author(s):  
Peng Qiao ◽  
Di Zhang ◽  
Song Zeng ◽  
Yicun Wang ◽  
Biao Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Biochemical Recurrence ◽  
Surgical Margin ◽  
Gene Expression Omnibus ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Support Vector ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Aim: This study aims to identify novel marker to predict biochemical recurrence (BCR) in prostate cancer patients after radical prostatectomy with negative surgical margin. Materials & methods: The Cancer Genome Atlas database, Gene Expression Omnibus database and Cancer Cell Line Encyclopedia database were employed. The ensemble support vector machine-recursive feature elimination method was performed to select crucial gene for BCR. Results: We identified MYLK as a novel and independent biomarker for BCR in The Cancer Genome Atlas training cohort and confirmed in four independent Gene Expression Omnibus validation cohorts. Multi-omic analysis suggested that MYLK was a DNA methylation-driven gene. Additionally, MYLK had significant positive correlations with immune infiltrations. Conclusion: MYLK was identified and validated as a novel, robust and independent biomarker for BCR in prostate cancer.

scholarly journals Gene Expression Changes Associated with Dedifferentiation in Liposarcoma Predict Overall Survival

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3049
Author(s):  
Nicholas Brian Shannon ◽  
Qiu Xuan Tan ◽  
Joey Wee-Shan Tan ◽  
Josephine Hendrikson ◽  
Wai Har Ng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Gene Signature ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Significant Difference ◽  
Cancer Genome Atlas ◽  
Well Differentiated ◽  
Multiple Recurrences ◽  
Laser Capture

Up to 10% of well-differentiated liposarcoma (WDLS) progress to dedifferentiated liposarcoma (DDLS). We aimed to identify gene expression changes associated with dedifferentiation and whether these were informative of tumour biology of DDLS. We analysed datasets from the Gene Expression Omnibus (GEO, ID = GSE30929) database to identify differentially expressed genes between WDLS (n = 52) and DDLS (n = 39). We validated the signature on whole and laser-capture microdissected samples from patients with tumours consisting of mixed WDLS and DDLS components. A subset of this signature was applied to an independent dataset from The Cancer Genome Atlas (TCGA, n = 58 DDLS) database to segregate samples based on gene expression and compared for recurrence and overall survival (OS). A 15-gene signature consisting of genes with increased expression in DDLS compared to WDLS was generated. This signature segregated WDLS and DDLS samples from patients with mixed component tumours and across multiple recurrences. A further subset of this signature, consisting of five genes (AQP7, ACACB, FZD4, GPD1, LEP), segregated DDLS in a TCGA cohort with a significant difference in OS (p = 0.019) and recurrence-free survival (RFS) (p = 0.061). The five-gene model stratified DDLS into prognostic groups and outperformed clinical factors in existing models in retroperitoneal DDLS.

Transcriptomic and Proteomic Analysis of Steatohepatitic Hepatocellular Carcinoma Reveals Novel Distinct Biologic Features

2020 ◽  
Vol 155 (1) ◽  
pp. 87-96
Author(s):  
Benjamin J Van Treeck ◽  
Taofic Mounajjed ◽  
Roger K Moreira ◽  
Mushfig Orujov ◽  
Daniela S Allende ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Carnitine Palmitoyltransferase ◽  
Cancer Genome ◽  
Hedgehog Pathway ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Abstract Objectives Steatohepatitic hepatocellular carcinoma is a distinct variant of hepatocellular carcinoma strongly associated with underlying nonalcoholic steatohepatitis. The molecular biology of steatohepatitic hepatocellular carcinoma is not fully elucidated, and thus we aimed to investigate the molecular underpinnings of this entity. Methods Transcriptomic analysis using RNAseq was performed on eight tumor-nonneoplastic pairs of steatohepatitic hepatocellular carcinoma with comparison to conventional hepatocellular carcinoma transcriptomes curated in The Cancer Genome Atlas. Immunohistochemistry was used to validate key RNA-level findings. Results Steatohepatitic hepatocellular carcinoma demonstrated a distinctive differential gene expression profile compared with The Cancer Genome Atlas curated conventional hepatocellular carcinomas (n = 360 cases), indicating the distinctive steatohepatitic hepatocellular carcinoma morphology is associated with a unique gene expression profile. Pathway analysis comparing tumor-nonneoplastic pairs revealed significant upregulation of the hedgehog pathway based on GLI1 overexpression and significant downregulation of carnitine palmitoyltransferase 2 transcript. Glutamine synthetase transcript was significantly upregulated, and fatty acid binding protein 1 transcript was significantly downregulated and immunohistochemically confirmed, indicating steatohepatitic hepatocellular carcinoma tumor cells display a zone 3 phenotype. Conclusions Steatohepatitic hepatocellular carcinoma demonstrates a distinctive morphology and gene expression profile, phenotype of zone 3 hepatocytes, and activation of the hedgehog pathway and repression of carnitine palmitoyltransferase 2, which may be important in tumorigenesis.

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