Significant expression of CHK1 and p53 in bladder urothelial carcinoma as potential therapeutic targets and prognosis

Zheng, Linfeng; Zhu, Yumeng; Lei, Lei; Sun, Weibo; Cheng, Guoping; Yang, Shifeng

doi:10.3892/ol.2017.7344

Cited by 9 publications

(8 citation statements)

References 29 publications

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“…TP53 gene variants were reported in our study at similar frequency to TERT gene variants. TP53 genetic variants were reported in SR-SCCUB and conventional UC and were associated with inferior survival outcomes in both histologies [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Genomic characterization of non-schistosomiasis-related squamous cell carcinoma of the urinary bladder: A retrospective exploratory study

et al. 2021

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Background Non-schistosomiasis related-squamous cell carcinoma of urinary bladder (NSR-SCCUB) is a rare tumor subtype distinct from urothelial carcinoma (UC). Studies assessing molecular biomarkers in bladder cancer have generally focused on UC, and genomic data of NSR-SCCUB is limited. We aim to provide additional insight into the molecular underpinnings of this rare entity. Methods NSR-SCCUB patients were identified retrospectively at Princess Margaret Cancer Centre between 2002 and 2017. Demographics, disease characteristics, therapeutic approaches, and outcomes were collected. Tissue samples were interrogated using the Oncomine Comprehensive Assay v3 (ThermoFisher). Kaplan-Meier method was used to estimate the disease-free survival and overall survival (OS). Results Overall, 11 patients with NSR-SCCUB were identified between 2002 and 2017 with adequate tissue samples. Median age was 71 years (45–86), predominantly male (63.6%). At time of diagnosis, 9 patients (81.8%) had muscle-invasive disease, 1 (9.1%) had non-muscle invasive, and 1 (9.1%) had advanced disease. Nine (81.8%) patients had radical cystectomy and pelvic lymph nodes dissection. Eight (72.7%) patients had pT3 or pT4 with N0, and 5 (45.5%) were grade 3. Median OS was 12.5 months (95% CI 7.7–17.2 months). Single nucleotide variants or insertion/deletions were identified in TP53, TERT, PIK3CA, PTEN, CREBBP, FBXW7, and FGFR3. Amplifications were found in CCND1, and EGFR. Conclusions NSR-SCCUB has potentially actionable genomic alterations with anticancer agents and many of these aberrations are also seen in UC. The recruitment of NSR-SCCUB patients harboring such mutations should be considered in biomarker driven urinary bladder cancer studies.

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Section: Discussionmentioning

confidence: 99%

Genomic characterization of non-schistosomiasis-related squamous cell carcinoma of the urinary bladder: A retrospective exploratory study

et al. 2021

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“…Due to its anti-injury effect, CHEK1 plays an important role in tumor development and apoptosis [ 63 – 65 ]. Many studies have reported that CCNB1, CCNB2, and CHEK1 were involved in p53 signaling pathway [ 66 – 68 ]. We found that mRNA levels of three p53 markers including CCNB1, CCNB2, and CHEK1 were significantly upregulated in 20 HCC tumor tissues versus nontumor adjacent tissues by bioinformatics analysis and experimental verification, and their mRNA expression levels were all negatively correlated with HCC patients' survival rates (p<0.001).…”

Section: Discussionmentioning

confidence: 99%

Analysis of Transcription Factor-Related Regulatory Networks Based on Bioinformatics Analysis and Validation in Hepatocellular Carcinoma

Shui

Yao

Zhang

et al. 2018

BioMed Research International

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Hepatocellular carcinoma (HCC) accounts for a significant proportion of liver cancer, which has become the second most common cause of cancer-related mortality worldwide. To investigate the potential mechanisms of invasion and progression of HCC, bioinformatics analysis and validation by qRT-PCR were performed. We found 237 differentially expressed genes (DEGs) including EGR1, FOS, and FOSB, which were three cancer-related transcription factors. Subsequently, we constructed TF-gene network and miRNA-TF-mRNA network based on data obtained from mRNA and miRNA expression profiles for analysis of HCC. We found that 42 key genes from the TF-gene network including EGR1, FOS, and FOSB were most enriched in the p53 signaling pathway. The qRT-PCR data confirmed that mRNA levels of EGR1, FOS, and FOSB all were decreased in HCC tissues. In addition, we confirmed that the mRNA levels of CCNB1, CCNB2, and CHEK1, three key markers of the p53 signaling pathway, were all increased in HCC tissues by bioinformatics analysis and qRT-PCR validation. Therefore, we speculated that miR-181a-5p, which was upregulated in HCC tissues, could regulate FOS and EGR1 to promote the invasion and progression of HCC by p53 signaling pathway. Overall, the study provides support for the possible mechanisms of progression in HCC.

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“…DNA damage response is a complex signaling network involving cell cycle checkpoints as well as DNA damage and repair pathways. 43 Herein, 14 molecular changes in gene/protein groups and altered genes/proteins, such as tumor suppressor, antiapoptotic, cyclin, monooxigenase, glycosidase, enzyme binding, transferase, DNA binding, hydrolase, helicase, ribonucleoprotein, exonuclease, endonuclease, and translocase were examined. Meta-analysis for GSTM1 and GSTT1, as well as for transferase and hydrolase groups, showed no significant difference between smokers and non-smokers regarding the damage/polymorphism of these proteins.…”

Section: Uncertain Risk Of Bias Low Risk Of Biasmentioning

confidence: 99%

Effects of tobacco on the DNA of smokers and non-smokers affected by OSCC: systematic review and meta-analysis

et al. 2023

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Scientific evidence about genetic and molecular changes in oral squamous cell carcinoma (OSCC) among smokers and non-smokers is inconclusive. This systematic review and meta-analysis assessed the effects of tobacco on the DNA of individuals with OSCC based on protein mutations. Electronic searches were conducted on PubMed, Ovid, Web of Science, and Scopus to identify observational studies published up to January/2022. The Joanna Briggs Institute tool was used for the critical appraisal of studies. The certainty of the evidence was evaluated. Twenty-three studies assessing 4,060 individuals (2,967 smokers vs. 1,093 non-smokers) were included in this review. Fifteen groups of proteins/genes were investigated. Analysis of the quality of articles revealed low risk of bias in most studies. The certainty of the evidence was very low. The meta-analysis confirmed no significant difference between smokers and non-smokers with respect to damage to GSTM1 (OR: 0.60; 95%CI: 0.30-1.18), GSTT1 (OR: 1.18; 95%CI:0.49-2.83), hydrolase proteins (Ku70 and Ku80) (OR: 0.74; 95%CI: 0.18-3.05), and transferase proteins (GSTM1, GSTT1, GSTM3) (OR: 0.74; 95%CI: 0.47-1.18). Most of the studies included showed that smokers are more likely to exhibit genetic instability. However, the meta-analysis revealed that smokers do not necessarily have more genetic alterations in the DNA than non-smokers.

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Significant expression of CHK1 and p53 in bladder urothelial carcinoma as potential therapeutic targets and prognosis

Cited by 9 publications

References 29 publications

Genomic characterization of non-schistosomiasis-related squamous cell carcinoma of the urinary bladder: A retrospective exploratory study

Genomic characterization of non-schistosomiasis-related squamous cell carcinoma of the urinary bladder: A retrospective exploratory study

Analysis of Transcription Factor-Related Regulatory Networks Based on Bioinformatics Analysis and Validation in Hepatocellular Carcinoma

Effects of tobacco on the DNA of smokers and non-smokers affected by OSCC: systematic review and meta-analysis

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