FATS expression is associated with cisplatin sensitivity in non small cell lung cancer

Abstract

BackgroundAlthough the survival benefit of cisplatin-based adjuvant chemotherapy has been proven for patients with non small cell lung cancer (NSCLC), the resistance to cisplatin and its dose-dependent side effects remain a challenge. Improvement in survival and reduction of side effects require a biomarker capable of defining the response to cisplatin treatments in patients with NSCLC. FATS is a newly identified tumor suppressor involved in DNA damage-induced carcinogenesis. In this study, we investigated whether the quantified mRNA expression of FATS can predict cisplatin sensitivity in NSCLC. MethodsThe expression level of FATS mRNA in tumor samples from patients receiving an initial diagnosis of NSCLC (n=89) was determined by quantitative real-time reverse transcription PCR. The histological characteristics of patients were retrospectively reviewed. Cisplatin-induced apoptosis in NSCLC cells was evaluated by flow cytometry after Annexin V staining. ResultsThe mRNA level of FATS was significantly downregulated in NSCLC samples compared with normal tissues from the same patient (P=0.001). Low level of FATS mRNA expression was correlated with poor overall survival in NSCLC (P=0.030). For those NSCLC patients receiving cisplatin-based chemotherapy, the overall survival was significantly longer in FATS-high subgroup than that in FATS-low subgroup (P=0.038). Multivariate analysis revealed the independent value of FATS mRNA in predicting the overall survival for NSCLC patients receiving cisplatin-based chemotherapy. Furthermore, enhanced expression of FATS significantly sensitized NSCLC cells to cisplatin-induced apoptosis. ConclusionThe relatively high expression of FATS mRNA provides a new biomarker for a good outcome in patients receiving cisplatin-based chemotherapy.