Correlation of BRCA1, TXR1 and TSP1 mRNA expression with treatment outcome to docetaxel-based first-line chemotherapy in patients with advanced/metastatic non-small-cell lung cancer.

ABSTRACT

BACKGROUND: We explored the predictive significance of BRCA1, TXR1 and TSP1 expression in non-small-cell lung cancer (NSCLC) patients treated with docetaxel in association with cisplatin or gemcitabine. METHODS: To analyse BRCA1, TXR1 and TSP1 mRNA expression from microdissected primary tumours of 131 patients with stage IIIB (wet) and IV NSCLC, RT-qPCR was used. RESULTS: The mRNA levels of TXR1/TSP1 were inversely correlated (Spearman's test -0.37; P=0.001). Low TXR1 mRNA levels were associated with higher response rate (RR; P=0.018), longer median progression-free survival (PFS; P=0.029) and median overall survival (mOS P=0.003), whereas high TSP1 expression was correlated with higher RR (P=0.035), longer PFS (P<0.001) and mOS (P<0.001). Higher BRCA1 mRNA expression was associated with higher RR (P=0.028) and increased PFS (P=0.021), but not mOS (P=0.4). Multivariate analysis demonstrated that low TXR1/high TSP1 expression was an independent factor for increased PFS (HR 0.49; 95% CI 0.32-0.76; P<0.001) and mOS (HR 0.37; 95% CI 0.2-0.58; P<0.001), whereas high BRCA1 expression was correlated with increased PFS (HR 0.53; 95% CI 0.37-0.78; P=0.001). CONCLUSIONS: These data indicate that TXR1/TSP1 and BRCA1 expression could be used for the prediction of taxanes' resistance in the treatment of NSCLC.