Abstract: Background and purpose: BIM gene and Scribble are important mediators involved in cell death. BIM isoform without BH3-only domain blocks apoptosis in cancer cells. Deregulated Scribble expression contributes to tumorigenesis including proliferation, invasion, metastasis and drug resistance in various epithelial cancers. We explored the impacts of BIM polymorphism and Scribble expression on treatment effect of advanced non-small cell lung cancer (NSCLC) with chemotherapy. Methods: Ninety-six patients with advanced NSCLC who received platinum-based chemotherapy in Zhongshan Hospital, Fudan University from Jan. 2014 to Dec. 2015 were enrolled. Polymerase chain reaction (PCR) was used to detect BIM gene polymorphism in NSCLC patients. Immunohistochemistry was used to detect the expression level of Scribble in specimens. BIM gene polymorphism and Scribble expression were correlated with treatment outcome from chemotherapy. Results: Among patients who received chemotherapy, the median progression-free survival (PFS) were 5.0 and 2.7 months for patients with wild-type BIM gene and BIM gene deletion polymorphism, respectively (P=0.010). Patients with Scribble high expression had significantly longer median PFS than those with Scribble low expression (7.0 months vs 4.0 months, P<0.001). Patients with wild-type BIM gene and Scribble high expression had significantly longer median PFS than those with wild-type BIM gene or Scribble high expression, and those with BIM gene deletion polymorphism and Scribble low expression (10.0 months vs 4.5 months vs 2.0 months, P<0.001). Multivariate analysis showed that BIM gene deletion and Scribble low expression were independent indicators of shorter PFS (HR=3.221, P<0.001; HR=3.312, P<0.001). Conclusion: BIM gene deletion and Scribble low expression predict shorter PFS to chemotherapy. BIM combined with Scribble have better predictive value.

Key words: BIM Gene, Scribble, Non-small cell lung cancer, Chemotherapy