Predictive value of APE1, BRCA1, ERCC1 and TUBB3 expression in patients with advanced non-small cell lung cancer (NSCLC) receiving first-line platinum–paclitaxel chemotherapy

Zheng, Liping; Qu, Yi; Guan, Wei; Li, Mengxia; Peng, Yu; Shiheng, Zhang; Xiong, Yanli; Wang, Dong

doi:10.1007/s00280-014-2562-1

Cited by 46 publications

(41 citation statements)

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“…In our study, APE1 positive expression was also tested to correlate with poor overall survival in Chinese patient cohort. Al-Attar et al reported that APE1 expression associated with poor survival in patients with ovarian, gastro-oesophageal and pancreatic cancers, being considering as a potential drug target [20]. Multiple studies elucidated that as predictors of gastric cancer risk, APE1 ploymorphism and protein expression present a positive relationship with prognosis of gastric carcinoma [19–21].…”

Section: Discussionmentioning

confidence: 99%

AT101 exerts a synergetic efficacy in gastric cancer patients with 5-FU based treatment through promoting apoptosis and autophagy

et al. 2016

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Gastric cancer remains a disease with a high mortality rate despite of multiple therapeutic strategies. So far, it is very important to develop new treatment approaches to improve current therapeutic efficacy in gastric cancer. Apurinic/apyrimidinic endonuclease (APE1) involves in DNA base excision repair (BER) during DNA damage pathway. APE1 was found to be associated with poor overall survival with gastric cancer patients. In the in vitro experiment, we tested APE1 inhibitor-AT101 could potently inhibit gastric cancer cell growth and further induce cancer cell apoptosis and autophagy through p53-dependent pathway. Downregulation of APE1 by AT101 has ability to suppress gastric cancer cell migration and renewal through inhibition of CD133, Nanog and LC3expression. Based on findings that Her-2 positive expression cases has poor prognosis from our dataset and TCGA database, we investigated the role of AT101 in synergetic efficacy with 5-FU treatment in Her-2 overexpression gastric cancer in vivo, indicating that AT101 is able to enhance 5-FU in the shrinkage of xenograft mice tumor and induction of cell apoptosis. In summary, the data obtained from our study showed APE1 is guided as a potential therapeutic target for gastric cancer. AT101 could be regarded as a potent inhibitor to promote chemotherapeutic sensitivity in patients with gastric cancer.

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Section: Discussionmentioning

confidence: 99%

AT101 exerts a synergetic efficacy in gastric cancer patients with 5-FU based treatment through promoting apoptosis and autophagy

et al. 2016

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“…The IHC was performed to determine APE1 expression in NSCLC tissues described previously [24]. Protein was scored for four categories, i.e., score 0, no expression in tumor cells; score 1+, faint/barely perceptible partial nuclear expression in < 10% of tumor cells; score 2+, weak to moderate expression of the entire nucleus in > 10% of tumor cells; and score 3+, strong expression of the entire nucleus in > 10% of tumor cells.…”

Section: Methodsmentioning

confidence: 99%

Serum APE1 as a predictive marker for platinum-based chemotherapy of non-small cell lung cancer patients

Zhang

Dai

et al. 2016

Oncotarget

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PurposeTo define the role of the DNA repair protein apurinic/apyrimidinic endonuclease 1 (APE1) in predicting the prognosis and chemotherapeutic response of non-small cell lung cancer patients receiving platinum-containing chemotherapy.ResultsOur investigations found that serum APE1 level was significantly elevated in 229 of 412 NSCLC patients and correlated with its level in tissue (r2 = 0.639, p < 0.001). The elevated APE1 level in both tissue and serum of patients prior to chemotherapy was associated with worse progression-free survival (HR: 2.165, p < 0.001, HR: 1.421, p = 0.012), but not with overall survival. After 6 cycles of chemotherapy, a low APE1 serum level was associated with better overall survival (HR: 0.497, p = 0.010).Experimental DesignWe measured APE1 protein levels in biopsy tissue from 172 NSCLC patients and sera of 412 NSCLC patients receiving platinum-based chemotherapy by immunohistochemistry and a newly established sensitive and specific enzyme-linked immunosorbent assay, respectively. APE1 levels in sera of 523 healthy donors were also determined as control.ConclusionsOur studies indicate that APE1 is a biomarker for predicting prognosis and therapeutic efficacy in NSCLC. The chemotherapy-naïve serum APE1 level, which correlated with its tissue level inversely associated with progression-free survival of platinum-containing doublet chemotherapy, whereas post-treatment serum APE1 level was inversely associated with overall survival.

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“…Nucleotide excision repair (NER) and base excision repair (BER) pathway are major DNA repair systems. Besides XRCC1, other DNA base excision repair genes including OGG1, [17] APE1, [17, 39–41] XRCC3, [42] PARP1, [43] were reported to be associated with clinical outcomes in NSCLC treated with platinum-based regimen. Genes involved in NER system such as ERCC1 [41, 43–45], ERCC2(XPD), [44, 46] BAG1, [46] XPA, [47] were also reported to be associated with clinical outcomes in NSCLC treated with platinum-based regimen.…”

Section: Discussionmentioning

confidence: 99%

“…Besides XRCC1, other DNA base excision repair genes including OGG1, [17] APE1, [17, 39–41] XRCC3, [42] PARP1, [43] were reported to be associated with clinical outcomes in NSCLC treated with platinum-based regimen. Genes involved in NER system such as ERCC1 [41, 43–45], ERCC2(XPD), [44, 46] BAG1, [46] XPA, [47] were also reported to be associated with clinical outcomes in NSCLC treated with platinum-based regimen. In addition, association between BRCA1, [41, 45] MDR1, [48] eIF3a, [49, 50] PKM2, [51] and clinical outcomes in NSCLC treated with platinum-based regimen were also investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Genes involved in NER system such as ERCC1 [41, 43–45], ERCC2(XPD), [44, 46] BAG1, [46] XPA, [47] were also reported to be associated with clinical outcomes in NSCLC treated with platinum-based regimen. In addition, association between BRCA1, [41, 45] MDR1, [48] eIF3a, [49, 50] PKM2, [51] and clinical outcomes in NSCLC treated with platinum-based regimen were also investigated. Li P’s research demonstrated the combined effects of BAG1 and XPD polymorphisms on chemotherapy sensitivity and survival in patients with advanced NSCLC.…”

Section: Discussionmentioning

confidence: 99%

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Association between the XRCC1 polymorphisms and clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy: a meta-analysis based on the PRISMA statement

Xiao

2017

BMC Cancer

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BackgroundBase excision repair (BER) pathway is a DNA repair pathway that is important in carcinogenesis and in response to DNA-damaging chemotherapy. XRCC1 is one of important molecular markers for BER. So far, the role of XRCC1 polymorphisms with clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy is inconclusive. To explore the relationship between XRCC1 polymorphisms and platinum-based chemotherapy in advanced NSCLC patients, we performed this meta-analysis.MethodsCrude odds ratios (ORs), Cox proportional hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) were adopted to assess the strength of association between XRCC1 polymorphisms and response rate, Overall survival (OS) and progression free survival (PFS) of advanced NSCLC treated with platinum-based chemotherapy. Q test and I 2 test were used for the assessment of heterogeneity. Subgroup analyses were conducted when heterogeneity exists. Begg’s funnel plots and Egger’s linear regression test were used to estimate publication bias. Sensitivity analysis was performed to evaluate the stability of the result.ResultsA total of 19 studies including 2815 individuals were eligible for the analysis, results showed XRCC1 194Arg allele was negatively associated with the objective response rate relative to 194Trp, and results of homozygous model, dominant model and heterozygous model suggested a gene dosage effect negative correlation between 194Arg allele and objective response rate(ArgArg vs TrpTrp: OR = 0.64(95%CI: 0.44-0.91); ArgArg + TrpArg vs TrpTrp: OR = 0.79(95%CI: 0.57-1.11); TrpArg vs TrpTrp: OR = 1.05(95%CI: 0.73-1.51)). XRCC1 399Gln may indicate favorable overall survival (GlnGln + GlnArg vs ArgArg: HR = 0.65(95%CI: 0.43–0.98)) and favorable PFS (GlnGln vs ArgArg: HR = 0.72(95%CI: 0.48–0.97)) in Asian patients; while in Caucasian patients, XRCC1 399Gln indicated poorer overall survival (GlnGln vs ArgArg: HR = 2.29(95%CI: 1.25–3.33)).ConclusionsOur results indicated that in NSCLC patients treated with platinum-based regimen, XRCC1 194Arg allele suggest poor objective response rate, the GlnGln genotype of XRCC1 399 suggest poorer overall survival in Caucasian patients, and longer PFS in Asian patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3487-y) contains supplementary material, which is available to authorized users.

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Predictive value of APE1, BRCA1, ERCC1 and TUBB3 expression in patients with advanced non-small cell lung cancer (NSCLC) receiving first-line platinum–paclitaxel chemotherapy

Abstract: The data indicate that APE1, ERCC1 and TUBB3 could be a useful biomarker to predict clinical outcome in patients with advanced NSCLC receiving first-line platinum-paclitaxel chemotherapy.

Cited by 46 publications

References 46 publications

AT101 exerts a synergetic efficacy in gastric cancer patients with 5-FU based treatment through promoting apoptosis and autophagy

AT101 exerts a synergetic efficacy in gastric cancer patients with 5-FU based treatment through promoting apoptosis and autophagy

Serum APE1 as a predictive marker for platinum-based chemotherapy of non-small cell lung cancer patients

Association between the XRCC1 polymorphisms and clinical outcomes of advanced NSCLC treated with platinum-based chemotherapy: a meta-analysis based on the PRISMA statement

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