Effects of JWA, XRCC1 and BRCA1 mRNA expression on molecular staging for personalized therapy in patients with advanced esophageal squamous cell carcinoma

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.

Combination of histoculture drug response assay and qPCR as an effective method to screen biomarkers for personalized chemotherapy in esophageal cancer

“…Conversely, high BRCA1 expression was also positively associated with clinical outcomes in those who received docetaxel-fluorouracil chemotherapy. As a dual predictive biomarker, the results were consistent with previous findings by the present authors (40,41). The findings supported the hypothesis that the use of a combination of HDRA and qPCR is able to effectively distinguish biomarkers in their ability to evaluate response to chemotherapy.…”

Identification of distinct mutational patterns and new driver genes in oesophageal squamous cell carcinomas and adenocarcinomas

“…As a validation, all existing clinical prognostic parameters, including primary tumour size, lymph node involvement, as well as distant metastasis were strongly associated with patients’ overall survival (online supplementary figure 6 ), confirming that the combined cohort was valid for assessing prognostic biomarkers. We found that mutations of several driver genes (all SMGs except for BRCA1 , which was tested because it has been associated with treatment response and survival in oesophageal cancer 26–28 ) were associated with patients’ outcome in univariate log-rank analysis, including EP300, AJUBA and BRCA1 in OSCC, and FBXW7 and PTEN in OAC ( figure 3A , online supplementary figure 6 ). EP300 mutation and PTEN protein loss were observed to have significant detrimental effects on survival in independent OSCC and OAC cohorts, 8 29 respectively, supporting the present finding.…”

Apatinib suppresses tumor progression and enhances cisplatin sensitivity in esophageal cancer via the Akt/β-catenin pathway

“…Also, we obtained 25 advanced or metastatic cases (stage III or IV) treated with first-line cisplatin-based regimen, and their median age was 61 (48-81 years) and 16 cases were male. Treatment outcome was evaluated according to the Response Evaluation Criteria Evaluation in Solid Tumors (RECIST) system [18]. All patients signed their informed consent.…”