Abstract
BackgroundDNA damage repair genes JWA, XRCC1 and BRCA1 were associated with clinical outcomes and could convert the response to the cisplatin-based therapy in some carcinomas. The synergistic effects of JWA, XRCC1 and BRCA1 mRNA expression on personalized therapy remain unknown in advanced esophageal squamous cell carcinoma (ESCC).MethodsWe employed quantitative real-time polymerase chain reaction (qPCR) to determine the expression of JWA, XRCC1 and BRCA1 mRNA in paraffin-embedded specimen from 172 patients with advanced ESCC who underwent the first-line cisplatin-or docetaxel-based treatments.ResultsHigh JWA or XRCC1mRNA expression was correlated with longer median overall survival (mOS) in all the patients (both P < 0.001) or in subgroups with different regimens (all P < 0.05), but not correlated with response rate (RR, all P > 0.05). Multivariate analysis revealed that high JWA (HR 0.22; 95% CI 0.13-0.37; P < 0.001) or XRCC1 (HR 0.36; 95% CI 0.21-0.63; P < 0.001) mRNA expression emerged as the independent prognostic factors for ESCC patients in this cohort. But no significant difference in prognostic efficacy was found between JWA plus XRCC1 and JWA alone through ROC analysis. Further subgroup analysis showed cisplatin-based treatments could improve mOS of patients with low JWA expression (P < 0.05), especially in those with low BRCA1 expression simultaneously (P < 0.001); while in patients with high JWA expression, high BRCA1 mRNA expression was correlated with increased mOS in docetaxel-based treatments (P = 0.044).ConclusionJWA, XRCC1and BRCA1 mRNA expression could be used as predictive markers in molecular staging for personalized therapy in patients with advanced ESCC who received first-line cisplatin- or docetaxel-based treatments.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1364-0) contains supplementary material, which is available to authorized users.
Highlights
DNA damage repair genes JWA, XRCC1 and breast cancer susceptibility gene 1 (BRCA1) were associated with clinical outcomes and could convert the response to the cisplatin-based therapy in some carcinomas
73 patients treated with chemotherapy had stage III–IV and other 72 patients treated with chemoradiotherapy or radiotherapy alone had stage II–III at the time of diagnosis
After a median follow up period of 52.0 months, the median overall survival (mOS) was 13.0 months in chemotherapy group; while the mOS was 13.5 months after a median follow-up period 48.0 months in chemoradiotherapy group
Summary
DNA damage repair genes JWA, XRCC1 and BRCA1 were associated with clinical outcomes and could convert the response to the cisplatin-based therapy in some carcinomas. The synergistic effects of JWA, XRCC1 and BRCA1 mRNA expression on personalized therapy remain unknown in advanced esophageal squamous cell carcinoma (ESCC). We confirmed that JWA was a base excision repair (BER) protein which could regulate X-ray repair cross complement group 1(XRCC1) and participated in the DNA damage repair pathway through stabilizing BER protein complex to facilitate the repair of DNA single-strand breaks (SSB) [13]. The other DNA repair proteinBRCA1 which was involved in nucleotide excision repair (NER) and DNA double single break repair (DSBR) pathway was found to participate in the inverse resistance to cisplatin- or docetaxel-based treatments in patients with esophageal cancer [7,26]
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