&lt;p&gt;Berzosertib (VE-822) inhibits gastric cancer cell proliferation via base excision repair system&lt;/p&gt;

Ni, Fubiao; Tang, Hengjie; Wang, Cheng; Wang, Zixiang; Yu, Fangyi; Chen, Bicheng; Sun, Lu

doi:10.2147/cmar.s217375

“…NSUN2 high expression was also related to poor survival rates in hHNSCC [83], gastric cancer [79]. High NEIL1 expression is correlated with low overall survival in gastric cancer [84]. Consistency of our findings with earlier reports prompted us to check whether UHRF1, NSUN2, and NEIL1 expression levels of these genes are compatible with Gleason classifications.…”

Section: Discussionsupporting

confidence: 78%

UHRF1, NSUN2, and NEIL1 were Detected as Clinical Biomarker Candidates in Prostate Adenocarcinoma with Potential Roles in Disease Pathogenesis

Kahyaoğulları

¹

,

Demircan

²

2021

Preprint

0

View full text Add to dashboard Cite

Prostate cancer (PCa) is the most commonly diagnosed cancer in men. Expanding evidence suggests a significant association between cancer progression and RNA modifications. However, our knowledge of the link between m5C and hm5C pathways with PCa is limited. Therefore, we aimed to explore the diagnostic and prognostic values of m5C and hm5C regulators in PCa. In this study, genetic alterations in m5C and hm5C regulators were identified using publicly available databases. Differentially expressed genes in these pathways between tumor and nontumor samples, correlation among m5C and hm5C pathway members, and prognostic value of the regulators were evaluated. Furthermore, enrichment of gene ontology (GO) terms and KEGG pathways was carried out. Obtained results unveiled the mRNA level differences as the key genetic alterations for m5C and hm5C regulators between tumor and nontumor samples. UHRF1, TET3, and NEIL1 were significantly upregulated in tumor samples compared to nontumor ones, whereas EGR1 was significantly downregulated. UHRF1, DNMT1, NSUN2, NSUN4, C1orf77, C3orf37, WDR77, NEIL1, and TDG genes were identified as candidate prognostic markers of overall survival. The upregulated genes in patient samples with genetic alterations in m5C and hm5C pathways enriched cell cycle-related processes. In summary, our findings suggest that the m5C and hm5C regulators might play a role in PRAD development by activation of proliferation, and the UHRF1, NSUN2, and NEIL1 genes have the potential to be utilized as clinical biomarkers.

show abstract

“…Absence of base excision repair could result in the accumulation of DNA damage, leading to cancer malignant transformations and poor prognosis. This imbalance was also associated with DNA polymorphism regulation, and such uncorrected false DNA variant likely had relation to cancer risk [ 60 ]. The defects in nucleotide excision repair would lead to the increased instability of the genome.…”

Section: Discussionmentioning

confidence: 99%

Progressive and Prognostic Performance of an Extracellular Matrix-Receptor Interaction Signature in Gastric Cancer

Yang

¹

,

Chen

²

,

Mao

³

et al. 2020

View full text Add to dashboard Cite

The role of an extracellular matrix- (ECM-) receptor interaction signature has not been fully clarified in gastric cancer. This study performed comprehensive analyses on the differentially expressed ECM-related genes, clinicopathologic features, and prognostic application in gastric cancer. The differentially expressed genes between tumorous and matched normal tissues in The Cancer Genome Atlas (TCGA) and validation cohorts were identified by a paired t -test. Consensus clusters were built to find the correlation between clinicopathologic features and subclusters. Then, the least absolute shrinkage and selection operator (lasso) method was used to construct a risk score model. Correlation analyses were made to reveal the relation between risk score-stratified subgroups and clinicopathologic features or significant signatures. In TCGA (26 pairs) and validation cohort (134 pairs), 25 ECM-related genes were significantly highly expressed and 11 genes were downexpressed in gastric cancer. ECM-based subclusters were slightly related to clinicopathologic features. We constructed a risk score model = 0.081 ∗ log 2 CD 36 + 0.043 ∗ log 2 COL 5 A 2 + 0.001 ∗ log 2 ITGB 5 + 0.039 ∗ log 2 SDC 2 + 0.135 ∗ log 2 SV 2 B + 0.012 ∗ log 2 THBS 1 + 0.068 ∗ log 2 VTN + 0.023 ∗ log 2 VWF . The risk score model could well predict the outcome of patients with gastric cancer in both training ( n = 351 , HR: 1.807, 95% CI: 1.292-2.528, P = 0.00046 ) and validation ( n = 300 , HR: 1.866, 95% CI: 1.347-2.584, P = 0.00014 ) cohorts. Besides, risk score-based subgroups were associated with angiogenesis, cell adhesion molecules, complement and coagulation cascades, TGF-beta signaling, and mismatch repair-relevant signatures ( P < 0.0001 ). By univariate (1.845, 95% CI: 1.382-2.462, P < 0.001 ) and multivariate (1.756, 95% CI: 1.284-2.402, P < 0.001 ) analyses, we regarded the risk score as an independent risk factor in gastric cancer. Our findings revealed that ECM compositions became accomplices in the tumorigenesis, progression, and poor survival of gastric cancer.

show abstract

“…Biological function of BER removed these frequently produced lesions, maintained genomic integrity and affected the clinical prognosis and overall survival of gastric cancer according to the promotion of DNA repair capacity [33]. In previous study, the aurthor could regulate the base excision repair system to inhibite the growth of gastric cancer and provide the novel perspectives to evluate gastric cancer progression based on the role of base excision repair [34].…”

Section: Discussionmentioning

confidence: 98%

Expression of ASPN with Prognostic Values in Gastric Cancer: A Study Based on TCGA Data

Wc

¹

,

Xu

²

,

H

³

et al. 2021

Preprint

0

View full text Add to dashboard Cite

Objective: Gastric ancer is a common cancer with high cancer-related death in the world Although, ASPN has been reported as a potential biomarker in some cancers, the relationship of ASPN and clinical pathologic features in gastric cancer has not been investigated thoroughly. Thus, the aim of study is to evaluate the function of ASPN in gastric cancer based on TCGA. Materials and methods: The gene expression data (407 cases, Workﬂow Type: HTSeq-Counts) and corresponding clinical information were downloaded from the TCGA Genomic Data Commons data portal. We performed the NES and nominal p value to evaluate the pathways enriched in each phenotype. Then, we analyzed the association with ASPN and clinicopathologic variables based on Wilcoxon signed-rank test and logistic regression. Result: We found that it was significantly different in ASPN expression between gastric cancer and normal tissue (P<0.001). High ASPN expression was signiﬁcantly associated with high stage (Odds ratio (OR)=3.656 for stage II vs stage I and OR=0.014 for stage III vs stage I), T classification (OR=13.304 for T2 vs T1, OR=20.769 for T3 vs T1 and OR=24.857 for T4 vs T1) (all p-values< 0.05). Univariate analysis revealed ASPN could result in poor overall survival with HR=1.004 and P=0.036. Besides, multivariate analysis indicated that ASPN expression was an independent risk factor for overall survival (HR:1.010, P=0.000), age (HR: 1.046, P=0.002) and gender (HR: 1.623, P=0.026). Besides, GSEA results showed that Pentose phosphate pathway, Base excision repair, Peroxisome, Protesome, Nucleotide excision repair, and Mismatch repair were differentially enriched in gastric cancer with high ASPN expression phentype. Conclusion: ASPN expression is higher in gastric cancer than normal tissues, and considered ASPN as a potential independent molecular marker for diagnosis and prognosis of GC.

show abstract

<p>Berzosertib (VE-822) inhibits gastric cancer cell proliferation via base excision repair system</p>

Cited by 15 publications

References 42 publications

UHRF1, NSUN2, and NEIL1 were Detected as Clinical Biomarker Candidates in Prostate Adenocarcinoma with Potential Roles in Disease Pathogenesis

UHRF1, NSUN2, and NEIL1 were Detected as Clinical Biomarker Candidates in Prostate Adenocarcinoma with Potential Roles in Disease Pathogenesis

Progressive and Prognostic Performance of an Extracellular Matrix-Receptor Interaction Signature in Gastric Cancer

Expression of ASPN with Prognostic Values in Gastric Cancer: A Study Based on TCGA Data

Contact Info

Product

Resources

About