Base excision repair pathway:<i>PARP1</i>genotypes as modulators of therapy response in cervical cancer patients

Nogueira, Augusto; Assis, Joana; Faustino, I.; Pereira, Deolinda; Catarino, Raquel; Medeiros, Rui

doi:10.1080/1354750x.2016.1204006

Cited by 8 publications

(6 citation statements)

References 53 publications

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“…It was reported that peri- and postmenopausal women carrying the C-allele of the PARP-1 Val762Ala polymorphism (rs1136410) present a statistically significant lower OS and disease-free survival (DFS) among those with early-stage cervical cancer. 31 In the previous meta-analysis, PARP-1 polymorphism (rs1136410: T > C) was also noted to be a risk factor for gastrointestinal cancers in an Asian population, but not in a Caucasian population. 32 PARP-1 would be an advantageous indicator of the disease for population studies.…”

Section: Discussionmentioning

confidence: 93%

PARP-1 serves as a novel molecular marker for hepatocellular carcinoma in a Southern Chinese Zhuang population

Dou

et al. 2017

Tumour Biol.

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PARP-1 (poly(ADP-ribose) polymerase-1) plays an important role in tumorigenesis. Since its effects on different populations are varied, this study investigated the impact of PARP-1 on primary hepatocellular carcinoma in a Southern Chinese Zhuang population. We assessed the global PARP-1 messenger RNA expression in patients with hepatocellular carcinoma using The Cancer Genome Atlas dataset. Increased PARP-1 expression, related to alpha-fetoprotein level, was observed. The area under the receiver operating characteristic curve value was 0.833. Kaplan-Meier survival curves indicated that higher PARP-1 expression was not correlated with poorer overall survival and recurrence-free survival. In a Zhuang population, PARP-1 messenger RNA and protein levels were increased in the hepatocellular carcinoma tissue and its adjacent liver tissues as assessed by quantitative polymerase chain reaction, immunohistochemistry, and western blotting. Higher PARP-1 level was associated with a higher tumor stage (p < 0.05), without correlation with age, gender, smoking, drinking, tumor size, serum alpha-fetoprotein level, hepatitis B virus infection, metastasis, and invasion (p > 0.05). Further analysis suggested that H2AX, a PARP-1 protein interaction partner, was coordinated with PARP-1 in hepatocellular carcinoma tumorigenesis. Overall, some new characteristics of PARP-1 expression were noted in the Zhuang population. PARP-1 is a novel promising diagnostic marker for hepatocellular carcinoma in the Southern Chinese Zhuang population.

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Section: Discussionmentioning

confidence: 93%

PARP-1 serves as a novel molecular marker for hepatocellular carcinoma in a Southern Chinese Zhuang population

Dou

et al. 2017

Tumour Biol.

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“…Similarly, in the present study, our results demonstrate a significant association between PARP1 rs1136410 and lymph node involvement in gallbladder cancer patients. However, a significant association was not found between genotypes of PARP1 rs1136410 and lymph node involvement in cervical cancer patients (Roszak et al , 2013; Nogueira et al , 2017).…”

Section: Discussionmentioning

confidence: 84%

PARP1 rs1136410 (A/G) polymorphism is associated with early age of onset of gallbladder cancer

Anjali

Singh

Kumar

et al. 2021

European Journal of Cancer Prevention

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Objectives Evaluation of the association of PARP1 rs1136410 (A/G) polymorphism with gallbladder cancer susceptibility and its prognosis in the Indian population of eastern Uttar Pradesh and western Bihar. Methods PARP1 rs1136410 was genotyped by PCR-RFLP and its association with the prognosis of gallbladder cancer patients were analyzed using Kaplan–Meier plot and log-rank tests. Results Our results demonstrate that minor allele G is more frequent in gallbladder cancer patients than controls. The frequencies of minor allele G and GG genotype are significantly associated with increased risk of gallbladder cancer. Our data suggest that the minor allele G and homozygous genotype GG are significant predisposing factors for the early age of onset of gallbladder cancer. Similarly, women patients having AG and GG genotypes demonstrate an increased risk of gallbladder cancer. The risk group genotypes (AG + GG) are significantly more frequent in patients with thick gallbladder wall, with jaundice and with the presence of lymph node than in patients with normal gallbladder wall thickness, without jaundice and absence of lymph node involvement. Survival analysis data suggest that patients with risk group genotype (AG + GG) presenting jaundice have shorter overall survival. Conclusion Our study suggests that the minor allele G of PARP1 rs1136410 (A/G) is a predisposing factor for gallbladder carcinogenesis and is significantly associated with early onset of the disease. Interestingly, the minor allele G is significantly more frequent in the patients with jaundice, lymph node metastasis and gallbladder wall thickness.

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“…Studies are currently being carried out to investigate potential suppressors of survival pathways and promoters of apoptotic pathways as novel chemotherapy approaches for the treatment of cervical cancer [ 33 ]. An association between poly ADP-ribose polymerase 1 (PARP1) Val762Ala polymorphism (rs1136410) and cancer therapy response has been identified, and PARP1 genotypes have been proposed to be an independent prognostic factor in cervical cancer [ 34 ]. In addition, it has been shown that PARP-1 inhibition may augment cisplatin cytotoxicity in cervical cancer cells by diminishing DNA repair and suppressing β-catenin signaling pathway [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

MAPK4 deletion enhances radiation effects and triggers synergistic lethality with simultaneous PARP1 inhibition in cervical cancer

Tian

Lou

Tian

et al. 2020

J Exp Clin Cancer Res

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Background Cervical cancer is one of the most common cancers among females worldwide and advanced patients have extremely poor prognosis. However, adverse reactions and accumulating resistance to radiation therapy require further investigation. Methods The expression levels of mitogen-activated protein kinase 4 (MAPK4) mRNA were analyzed by real-time PCR and its association with overall survival was analyzed using Kaplan-Mier method. Colony formation, immunofluorescence and western blotting were used to examine the effects of MAPK4 knockout or over-expression on cervical cancer cells after radiation treatment. Drug-sensitivity of cervical cancer cells to PARP1 inhibitors, olaparib or veliparib, was analyzed by CCK-8 cell viability assays, and the 50% inhibitory concentration (IC50) was quantified using GraphPad Prism. The functional effects of MAPK4 knockout on the sensitivity of cervical cancer to radiation treatment and PARP1 inhibitors were further examined using xenograft tumor mouse models in vivo. Results Cervical cancer patients with high MAPK4 mRNA expression have lower survival rate. After radiation treatment, the colony number of MAPK4 knockout cells was markedly reduced, and the markers for DNA double-chain breakage were significantly up-regulated. In addition, MAPK4 knockout reduced protein kinase B (AKT) phosphorylation, whereas its over-expression resulted in opposite effects. In MAPK4 KO cells with irradiation treatment, inhibition of AKT phosphorylation promoted DNA double-chain breakage. Constitutive activation of AKT (CA-AKT) increased the levels of phosphorylated-AKT (p-AKT), and DNA repair-related proteins, phosphorylated-DNA-dependent protein kinase (p-DNA-PK) and RAD51 recombinase (RAD51). Furthermore, MAPK4 knockout was found to affect the sensitivity of cervical cancer cells to poly ADP-ribose polymerase 1 (PARP1) inhibitors by activating the phosphorylation of AKT. Moreover, in vivo results demonstrated that MAPK4 knockout enhanced the sensitivity of cervical cancer to radiation and PARP1 inhibitors in mouse xenograft models. Conclusions Collectively, our data suggest that combined application of MAPK4 knockout and PARP1 inhibition can be used as therapeutic strategy in radiation treatment for advanced cervical carcinoma.

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Base excision repair pathway:PARP1genotypes as modulators of therapy response in cervical cancer patients

Abstract: This is the first study evaluating the effect of PARP1 Val762Ala polymorphism in treatment response in cervical cancer patients. PARP1 genotypes may contribute as an independent prognostic factor in cervical cancer, being useful in predicting the clinical outcome.

Cited by 8 publications

References 53 publications

PARP-1 serves as a novel molecular marker for hepatocellular carcinoma in a Southern Chinese Zhuang population

PARP-1 serves as a novel molecular marker for hepatocellular carcinoma in a Southern Chinese Zhuang population

PARP1 rs1136410 (A/G) polymorphism is associated with early age of onset of gallbladder cancer

MAPK4 deletion enhances radiation effects and triggers synergistic lethality with simultaneous PARP1 inhibition in cervical cancer

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