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

Abstract

Background: Although 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.

Methods: The 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.

Results: The 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.

Conclusion: The relatively high expression of FATS mRNA provides a new biomarker for a good outcome in patients receiving cisplatin-based chemotherapy.