Dataset Information

Diagnostic and prognostic value of WNT family gene expression in hepatitis B virus?related hepatocellular carcinoma.

ABSTRACT: The aim of the present study was to investigate the diagnostic and prognostic value of Wingless?type MMTV integration site (WNT) gene family expression in patients with hepatitis B virus (HBV)?related hepatocellular carcinoma (HCC). The clinical data of the patients and gene expression levels were downloaded from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Receiver operating characteristic curve analysis was used to investigate the diagnostic value of WNT genes. Cox proportional hazard regression analysis and Kaplan?Meier survival analysis were performed to evaluate the association of WNT gene expression level with overall survival (OS) and recurrence?free survival (RFS). A nomogram was constructed for the prediction of prognosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Diagnostic receiver operating characteristic curve analysis suggested that WNT2 had a high diagnostic value, with an area under the curve (AUC) of >0.800 (P<0.0001, AUC=0.810, 95% CI: 0.767?0.852). Survival analysis indicated that the expression level of WNT1 was significantly associated with OS and RFS (adjusted P=0.033, adjusted HR=0.607, 95% CI: 0.384?0.960; and adjusted P=0.007, adjusted HR=0.592, 95% CI: 0.404?0.868, respectively). In the TCGA validation cohort, we also observed that WNT2 was significantly differentially expressed between HCC tissues and adjacent non?tumor tissues, and WNT1 was associated with both the OS and RFS of HCC. Therefore, through the GSE14520 HBV?related HCC cohort we concluded that WNT2 may serve as a diagnostic biomarker and WNT1 may serve as a prognostic biomarker. These results may also be extended to TCGA HCC verification cohort.

SUBMITTER: Han Q

PROVIDER: S-EPMC6667889 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Diagnostic and prognostic value of WNT family gene expression in hepatitis B virus‑related hepatocellular carcinoma.

Han Quanfa Q Wang Xiangkun X Liao Xiwen X Han Chuangye C Yu Tingdong T Yang Chengkun C Li Guanghui G Han Bowen B Huang Ketuan K Zhu Guangzhi G Liu Zhengqian Z Zhou Xin X Su Hao H Shang Liming L Gong Yizhen Y Song Xiaowei X Peng Tao T Ye Xinping X

Oncology reports 20190705 3

The aim of the present study was to investigate the diagnostic and prognostic value of Wingless‑type MMTV integration site (WNT) gene family expression in patients with hepatitis B virus (HBV)‑related hepatocellular carcinoma (HCC). The clinical data of the patients and gene expression levels were downloaded from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Receiver operating characteristic curve analysis was used to investigate the diagnostic value of WNT genes. C ...[more]

PMID: 31322232

Similar Datasets

Project description:Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and a major cause of cancer involved death worldwide. Prognosis remains poor because of high recurrence rates and lack of effective relapse prevention strategies. Notch pathway plays an important role in tumor progression and metastasis, and it is associated with the prognosis of cancer. A total of 465 hepatitis B virus (HBV)-related HCC patients who underwent surgery were enrolled. Single nucleotide polymorphisms (SNP) of Notch pathway receptors were genotyped using Sanger DNA sequencing. Kaplan-Meier curves and the Cox proportional hazards regression model were adopted to analyze the association of polymorphisms and mRNA expression with clinical and pathological features, respectively. Four SNPs (rs1043996 in Notch3 and rs422951, rs520692, rs3830041 in Notch4) were significantly associated with overall survival (OS) (P = 0.023, P = 0.042, P = 0.028, and P = 0.001 respectively). Patients carrying the AA genotype in rs1043996 and TT/TC genotypes in rs422951 and rs520692 significantly decreased risks of death, compared to those carrying the AG/GG genotype in rs1043996 and CC genotype in rs422951 and rs520692, respectively. Patients carrying the TT genotype in rs3830041 showed poorer OS, compared with those carrying the TC/CC genotype. A haplotype block (rs422951 was in strong LD with rs520692, r2 = 0.843) was identified in Notch4. Notch3 mRNA expression significantly increased in tumor tissue, compared with nontumor normal tissue (P < 0.0001). Moreover, higher expression of Notch3 was associated with poorer OS (HR = 2.11, 95% CI = 1.32-3.37, P = 0.002) and shorter recurrence time of HBV-related HCC (HR = 1.96, 95% CI = 1.31-2.93, P = 0.001). Our findings collectively indicate that Notch receptors variants (rs1043996 in Notch3 and rs422951, rs520692, rs3830041 in Notch4) are independent predictive targets for OS in HBV-related HCC patients. Notch3 expression is a potential prognostic biomarker of OS and recurrence-free survival (RFS) prediction in HBV-related HCC patients following surgical treatment.

Project description:Background: A high mortality rate makes hepatocellular carcinoma (HCC) one of the most common types of cancer globally. 5-methylcytosine (m5C) is an epigenetic modification that contributes to the prognosis of several cancers, but its relevance to HCC remains unknown. We sought to determine if the m5C-related regulators had any diagnostic or prognostic value in HCC. Methods: M5C regulatory genes were screened and compared between HCC and normal tissue from The Cancer Genome Atlas (TCGA)and Gene Expression Omnibus (GEO) databases. Least absolute shrinkage and selection operator method (LASSO) and univariate Cox regression analysis of differentially expressed genes were then performed to identify diagnostic markers. A LASSO prognostic model was constructed using M5C regulatory genes with prognostic values screened by TCGA expression data. HCC patients were stratified based on risk score, then clinical characteristics analysis and immune correlation analysis were performed for each subgroup, and the molecular functions of different subgroups were analyzed using both Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA). The prognostic model was evaluated using univariate and multivariate Cox analyses as well as a nomogram. Molecular typing was performed according to m5C regulatory genes and immune checkpoint genes expression respectively, and clinical characterization and immune correlation analysis were performed for each subgroup. Results: M5C regulatory genes are expressed differently in HCC patients with different clinical and pathological characteristics, and mutations in these genes are frequent. Based on five m5C regulators (NOP2, NSUN2, TET1, YBX1, and DNMT3B), we constructed a prognostic model with high predictive ability. The risk score was found to be an independent prognostic indicator. Additionally, risk scores can also be applied in subgroups with different clinical characteristics as prognostic indicators. Conclusion: The study combined data from TCGA and GEO for the first time to reveal the genetic and prognostic significance of m5C-related regulators in HCC, which provides new directions for identifying predictive biomarkers and developing molecularly targeted therapies for HCC.

Dataset Information

Diagnostic and prognostic value of WNT family gene expression in hepatitis B virus?related hepatocellular carcinoma.

Publications

Diagnostic and prognostic value of WNT family gene expression in hepatitis B virus‑related hepatocellular carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets