Association of expression of p53, livin, ERCC1, BRCA1 and PARP1 in epithelial ovarian cancer tissue with drug resistance and prognosis

Zhang, Zhengmao; Dou, Xiao-Meng; Yang, Hongfang; Jia, Ling; Qin, Kaiyun; Gao, Xingshuang; Yang, Botao; Zhang, Wenzhe; Qin, Congying; Zhang, Fenghua; Shan, Baoen

doi:10.1016/j.prp.2019.152794

Cited by 17 publications

(17 citation statements)

References 46 publications

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“…Some studies have suggested that single nucleotide polymorphism (SNP) can change the expression of repair genes [ 37 – 39 ], while other studies have shown that abnormally hypermethylation in the promoter region can inhibit gene expression, which will subsequently lead to the occurrence of some diseases and tumors and the resistance of chemotherapeutic drugs [ 40 , 41 ]. ERCC1 gene is the dominant gene in NER and an important component of DNA damage identification and repair, of which the expression and single nucleotide polymorphism may affect platinum resistance and prognosis in patients with ovarian cancer [ 6 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…Meanwhile, patients with the treatment after the relapse tend to have resistance to platinum drugs [ 4 , 5 ]. If the drug resistance of ovarian cancer patients can be predicted before or at the initial stage of chemotherapy in order to adjust the chemotherapy scheme in time, the tumor remission rate can be enhanced, and the prognosis of patients can be improved [ 6 , 7 ]. Therefore, identifying the sensitivity of patients to platinum drugs is the key to effectively enhance the efficacy of chemotherapy for ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

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ERCC1 rs11615 polymorphism and chemosensitivity to platinum drugs in patients with ovarian cancer: a systematic review and meta-analysis

et al. 2021

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Objective To explore the relationship between ERCC1 rs11615 polymorphism and chemosensitivity to platinum drugs in ovarian cancer by the method of meta-analysis. Methods Pubmed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), and China Wanfang databases were comprehensively searched up to September 2020, to identify the relationship between ERCC1 rs11615 polymorphism and chemosensitivity of ovarian cancer. The data was analyzed by Stata 15.0 statistic software. Results A total of 10 published papers were included, including 1866 patients with ovarian cancer. The results showed that compared allele C at ERCC1 rs11615 locus with allele T, the pooled OR was 0.92 (95%CI:0.68 ~ 1.24, P > 0.05). There were no significant differences in recessive, dominant, homozygous, and heterozygous models. In accordance with a subgroup analysis of Ethnicity, all genotypes were statistically significant in the Asian population. In the allelic, dominant, recessive, homozygous and heterozygous models, the OR was 0.70 (95%CI:0.51 ~ 0.95), 0.20 (95%CI:0.07 ~ 0.56), 0.79 (95%CI:0.63 ~ 1.00), 0.21 (95%CI:0.07 ~ 0.59), 0.19 (95%CI:0.07 ~ 0.54), respectively, while in the Caucasian population, no statistically significant genotype was found. Conclusion The ERCC1 rs11615 polymorphism is associated with chemosensitivity in patients with ovarian cancer, especially in the Asian population, but not in the Caucasian population.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ERCC1 rs11615 polymorphism and chemosensitivity to platinum drugs in patients with ovarian cancer: a systematic review and meta-analysis

et al. 2021

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“…In OvCa, TP53 is closely related to the cell cycle, apoptosis, and microangiogenesis [ 42 ]. The expression of TP53 was significantly associated with overall poor survival and CA125 levels in OvCa [ 43 ]. The FAS gene is the most important gene for regulating apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology-Based and Clinically Relevant Prediction of the Potential Targets of Chinese Herbs in Ovarian Cancer Patients

Sun

Liu

Liú

et al. 2020

BioMed Research International

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Reports increasingly suggest that Chinese herbal medicine (CHM) has been used to treat ovarian cancer (OvCa) with a good curative effect; however, the molecular mechanisms underlying CHM are still unclear. In this retrospective study, we explored CHM’s molecular targets for the treatment of OvCa based on clinical data and network pharmacology. We used the Kaplan-Meier method and Cox regression analysis to verify the survival rate of 202 patients with CHM-treated OvCa. The association between CHM and survival time was analyzed by bivariate correlation. A target network of CHM active ingredients against OvCa was established via network pharmacology. Cox regression analysis showed that CHM is an independent favorable prognostic factor. The median survival time was 91 months in the CHM group and 65 months in the non-CHM group. The survival time of FIGO stage III patients in the two groups was 91 months and 52 months, and the median survival period of FIOG stage IV patients was 60 months and 22 months, respectively ( p < 0.001 ). Correlation analysis demonstrated that 12 herbs were closely associated with prognosis, especially in regard to the long-term benefits. Bioinformatics analysis indicated that the anti-OvCa activity of these 12 herbs occurs mainly through the regulation of apoptosis-related protein expression, which promotes OvCa cell apoptosis and inhibits OvCa development. They also regulate the progress of OvCa treatment by promoting or inhibiting protein expression on the p53 signaling pathway and by inhibiting the NF-κB signaling pathway by directly inhibiting NF-κB.

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“…ERCC1 is the protein most investigated as a read-out of NER repair in different tumor types, including ovarian carcinoma, but with very contrasting results [ 41 , 42 , 43 , 44 ]. Stefensen et al [ 43 ] reported how tumors with negative ERCC1 expression had responded more to platinum-based therapy than ERCC1-positive tumors and these findings were associated with significant differences in progression-free survival, in both univariate ( p = 0.0012) and multivariate analysis ( p = 0.006).…”

Section: Discussionmentioning

confidence: 99%

Impact of ERCC1, XPF and DNA Polymerase β Expression on Platinum Response in Patient-Derived Ovarian Cancer Xenografts

Guffanti

Alvisi

Caiola

et al. 2020

Cancers

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Platinum resistance is an unmet medical need in ovarian carcinoma. Molecular biomarkers to predict the response to platinum-based therapy could allow patient stratification and alternative therapeutic strategies early in clinical management. Sensitivity and resistance to platinum therapy are partially determined by the tumor’s intrinsic DNA repair activities, including nucleotide excision repair (NER) and base excision repair (BER). We investigated the role of the NER proteins—ERCC1, XPF, ERCC1/XPF complex—and of the BER protein DNA polymerase β, as possible biomarkers of cisplatin (DDP) response in a platform of recently established patient-derived ovarian carcinoma xenografts (OC-PDXs). ERCC1 and DNA polymerase β protein expressions were measured by immunohistochemistry, the ERCC1/XPF foci number was detected by proximity ligation assay (PLA) and their mRNA levels by real-time PCR. We then correlated the proteins, gene expression and ERCC1/XPF complexes with OC-PDXs’ response to platinum. To the best of our knowledge, this is the first investigation of the role of the ERCC1/XPF complex, detected by PLA, in relation to the response to DDP in ovarian carcinoma. None of the proteins in the BER and NER pathways studied predicted platinum activity in this panel of OC-PDXs, nor did the ERCC1/XPF foci number. These results were partially explained by the experimental evidence that the ERCC1/XPF complex increases after DDP treatment and this possibly better associates with the cancer cells’ abilities to activate the NER pathway to repair platinum-induced damage than its basal level. Our findings highlight the need for DNA functional assays to predict the response to platinum-based therapy.

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Association of expression of p53, livin, ERCC1, BRCA1 and PARP1 in epithelial ovarian cancer tissue with drug resistance and prognosis

Cited by 17 publications

References 46 publications

ERCC1 rs11615 polymorphism and chemosensitivity to platinum drugs in patients with ovarian cancer: a systematic review and meta-analysis

ERCC1 rs11615 polymorphism and chemosensitivity to platinum drugs in patients with ovarian cancer: a systematic review and meta-analysis

Network Pharmacology-Based and Clinically Relevant Prediction of the Potential Targets of Chinese Herbs in Ovarian Cancer Patients

Impact of ERCC1, XPF and DNA Polymerase β Expression on Platinum Response in Patient-Derived Ovarian Cancer Xenografts

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