Use of tumoral expression TXR1 and TSP1 to predict overall survival of patients with non-small-cell-lung-cancer (NSCLC) treated with first line chemotherapy

Abstract

19011 Background: In vitro data suggestthat overexpression of TXR1 gene is associated with resistance to taxane-based chemotherapy, through downregulation of the thrombospondin 1 (TSP1) expression. The prognostic and predictive value of tumoral expression both genes were evaluated. Methods: Tumor samples from 80 chemotherapy-naïve patients, with stage IIIb (with pleural effusion) or IV NSCLC were prospectively collected. TXR1 and TSP1 mRNA levels were determined using quantitative real-time PCR from microdissected tumor cells derived from patients’ primary tumors. Results: Patients’ characteristics included median age 61 years, performance status 0–1(WHO) 95%, male 91%. Successful amplification could be performed in 78 (97%) patients. The tumoral mRNA levels of the two genes were inversely correlated (Spearman’s test: -0.54; p<0.001). Patients with low mRNA tumoral levels of TXR1 mRNA (n=39) had a significantly increased TTP (8.2 vs 2.5 months; p=0.04) and OS (19.4 vs 6.6 months; p=0.004) but there was no difference in response to treatment (RR) (42 vs 22%; p<0.09) in comparison with patients with high tumoral levels of TXR1 mRNA (n=39). Patients with tumoral TXR1 mRNA levels in the lower quartile (n=19) presented higher RR (42 vs 11%; p=0.034) in comparison with patients in the higher quartile (n=18). TSP1 overexpression was significantly correlated with increased OS (17.9 vs 9.2 months; p=0.02), but not with RR (33 vs 30%; p=0.8) and TTP (6.2 vs 2.7 months; p=0.154). Patients with high TSP1 and low TXR1 mRNA expression (n=31) presented prolonged OS (20.6 vs 7.5 months; p=0.006) and a trend for prolonged TTP (8.5 vs 2.5 months; p=0.06) when compared with patients with low TSP1 and high TTP1 mRNA expression (n=32). Conclusions: The tumoral mRNA expression of TXR1 merits further evaluation as a marker of resistance to taxanes treatment of NSCLC whereas the tumoral expression of TSP1 merits further evaluation as a prognostic marker for OS. No significant financial relationships to disclose.