Prognostic value of differentially methylated gene profiles in bladder cancer

Yang, Zeyu; Liu, Anwei; Xiong, Qiao; Xue, Yongping; Liu, Fei; Zeng, Shuxiong; Zhang, Zhensheng; Li, Yunfei; Sun, Yinghao; Xu, Chuanliang

doi:10.1002/jcp.28515

Cited by 12 publications

(7 citation statements)

References 20 publications

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“…ZNF667, encoding Zinc finger protein 667, may involve in transcription regulation, the aberrantly hypermethylation of which promoted progression of laryngeal and esophageal squamous cell carcinoma [31,32]. SOWAHC, encoding Ankyrin repeat domain-containing protein SOWAHC, is demonstrated to be prognostic in bladder cancer [33] and lung squamous cell carcinoma [34]. The 4 genes were selected as target genes in the following analysis, according to prognostic value in abovementioned studies and correlation with IGHV status in WGCNA.…”

Section: Resultsmentioning

confidence: 99%

HELQ and EGR3 expression correlate with IGHV mutation status and prognosis in chronic lymphocytic leukemia

Guo

Gao

et al. 2021

J Transl Med

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Background IGHV mutation status is a crucial prognostic biomarker for CLL. In the present study, we investigated the transcriptomic signatures associating with IGHV mutation status and CLL prognosis. Methods The co-expression modules and hub genes correlating with IGHV status, were identified using the GSE28654, by ‘WGCNA’ package and R software (version 4.0.2). The over-representation analysis was performed to reveal enriched cell pathways for genes of correlating modules. Then 9 external cohorts were used to validate the correlation of hub genes expression with IGHV status or clinical features (treatment response, transformation to Richter syndrome, etc.). Moreover, to elucidate the significance of hub genes on disease course and prognosis of CLL patients, the Kaplan–Meier analysis for the OS and TTFT of were performed between subgroups dichotomized by the median expression value of individual hub genes. Results 2 co-expression modules and 9 hub genes ((FCRL1/FCRL2/HELQ/EGR3LPL/LDOC1/ZNF667/SOWAHC/SEPTIN10) correlating with IGHV status were identified by WGCNA, and validated by external datasets. The modules were found to be enriched in NF-kappaB, HIF-1 and other important pathways, involving cell proliferation and apoptosis. The expression of hub genes was revealed to be significantly different, not only between CLL and normal B cell, but also between various types of lymphoid neoplasms. HELQ expression was found to be related with response of immunochemotherapy treatment significantly (p = 0.0413), while HELQ and ZNF667 were expressed differently between stable CLL and Richter syndrome patients (p < 0.0001 and p = 0.0278, respectively). By survival analysis of subgroups, EGR3 expression was indicated to be significantly associated with TTFT by 2 independent cohorts (GSE39671, p = 0.0311; GSE22762, p = 0.0135). While the expression of HELQ and EGR3 was found to be associated with OS (p = 0.0291 and 0.0114 respectively).The Kras, Hedgehog and IL6-JAK-STAT3 pathways were found to be associating with the expression of hub genes, resulting from GSEA. Conclusions The expression of HELQ and EGR3 were correlated with IGHV mutation status in CLL patients. Additionally, the expression of HELQ/EGR3 were prognostic markers for CLL associating with targetable cell signaling pathways.

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Section: Resultsmentioning

confidence: 99%

HELQ and EGR3 expression correlate with IGHV mutation status and prognosis in chronic lymphocytic leukemia

Guo

Gao

et al. 2021

J Transl Med

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“…At the same time, the methylation level of genes can effectively identify the degree of invasion of bladder tumors [25]. It is worth noting that based on TCGA data, the level of methylation and expression of SOWAHC is associated with prognosis [29]. HOXA9 promoter methylation has also been shown to be associated with an increase in recurrence and progression in NMIBC.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation-based classification and identification of bladder cancer prognosis-associated subgroups

et al. 2020

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Background: Bladder cancer (BCA) is the most common urinary tumor, but its pathogenesis is unclear, and the associated treatment strategy has rarely been updated. In recent years, a deeper understanding of tumor epigenetics has been gained, providing new opportunities for cancer detection and treatment. Methods: We identified prognostic methylation sites based on DNA methylation profiles of BCA in the TCGA database and constructed a specific prognostic subgroup. Results: Based on the consistent clustering of 402 CpGs, we identified seven subgroups that had a significant association with survival. The difference in DNA methylation levels was related to T stage, N stage, M stage, grade, sex, age, stage and prognosis. Finally, the prediction model was constructed using a Cox regression model and verified using the test dataset; the prognosis was consistent with that of the training set. Conclusions: The classification based on DNA methylation is closely related to the clinicopathological characteristics of BCA and determines the prognostic value of each epigenetic subtype. Therefore, our findings provide a basis for the development of DNA methylation subtype-specific therapeutic strategies for human bladder cancer.

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“…The penalty regularization parameter λ, which control the complexity of the signature, was obtained at minimum partial likelihood deviance . Further, R package Survminer (https://CRAN.R-project.org/package=survminer) was used to construct the final multivariate Cox survival risk model . Additionally, a nomogram based on the risk model and clinical factors was formulated .…”

Section: Methodsmentioning

confidence: 99%

A risk signature‐based on metastasis‐associated genes to predict survival of patients with osteosarcoma

Shi

Zhuang

et al. 2020

J of Cellular Biochemistry

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Osteosarcoma (OS) is the most common primary solid malignant bone tumor, and its metastasis is a prominent cause of high mortality in patients. In this study, a prognosis risk signature was constructed based on metastasis-associated genes. Four microarrays datasets with clinical information were downloaded from Gene Expression Omnibus, and 256 metastasis-associated genes were identified by limma package. Further, a protein-protein interaction network was constructed, and survival analysis was performed using data from the Therapeutically Applicable Research to Generate Effective Treatments data matrix, identifying 19 genes correlated with prognosis. Six genes were selected by the least absolute shrinkage and selection operator regression for multivariate cox analysis. Finally, a three-gene (MYC, CPE, and LY86) risk signature was constructed, and datasets GSE21257 and GSE16091 were used to validate the prediction efficiency of the signature. The survival times of low-and highrisk groups were significantly different in the training set and validation set.Additionally, gene set enrichment analysis revealed that the genes in the signature may affect the cell cycle, gap junctions, and interleukin-6 production. Therefore, the three-gene survival risk signature could potentially predict the prognosis of patients with OS. Further, proteins encoded by CPE and LY86 may provide novel insights into the prediction of OS prognosis and therapeutic targets.differentially expressed genes, metastasis, osteosarcoma, risk signature, survival analysis 1 | INTRODUCTION Osteosarcoma (OS), characterized by malignant mesenchymal cells producing an osteoid matrix and fibrillary stroma, is the most common osseous aggressive cancer in children and juveniles and commonly arises at the terminus of the long bones, including distal femurs, proximal tibias, and proximal humor. 1 According to the National Cancer Institute Surveillance, Epidemiology, and End Results program, the frequency of OS has increased by 0.3% per year over the last decade. 2 With the intensification of chemotherapeutic regimens, the 5-year survival rate of OS patients without metastasis has been improved to 60%-70%. 3 By contrast, the survival rate is only 0%-30% in patients with OS with metastasis, 4 indicating that OS metastasis is associated poor longterm prognosis. However, metastasis-associated molecules Yi Shi and Ronghan He contributed equally to this work.

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Prognostic value of differentially methylated gene profiles in bladder cancer

Cited by 12 publications

References 20 publications

HELQ and EGR3 expression correlate with IGHV mutation status and prognosis in chronic lymphocytic leukemia

HELQ and EGR3 expression correlate with IGHV mutation status and prognosis in chronic lymphocytic leukemia

DNA methylation-based classification and identification of bladder cancer prognosis-associated subgroups

A risk signature‐based on metastasis‐associated genes to predict survival of patients with osteosarcoma

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