The impact of Caspase-8 on non-small cell lung cancer brain metastasis in II/III stage patient

Abstract

The aim of this study is to evaluate the role of Caspase-8 in predicting non-small cell lung cancer (NSCLC) metastasis to brain. The expression of Caspase-8 was analyzed by immunohistochemistry in 203 surgical resected NSCLC patients, who were followed up. Caspase-8 expression level was correlated with clinicopathological characteristics. Time to brain metastasis (TTBM) was estimated using Kaplan-Meier method. Caspase-8 staining was predominantly located in the cell cytoplasm of NSCLC. ROC curve achieved a Sensitivity=94.7%, Specificity=48.9% and Negative Predictive Value=98.9% in diagnosing high and low risk groups to develop brain metastasis (BM). BM was indentified in 16.1% (18/112) patients in high Caspase-8 expression group, in contrast, only 1.1% (1/91) patients in low level group developed BM. There was a certain relation between Caspase-8 level and lymph node metastasis (P=0.08); Caspase-8 expression level significantly elevated in high BM risk group (P=0.00). Multivariate logistic regression analysis revealed that there was ignificant correlation only between Caspase-8 and BM. Univariate and multivariable Cox regression analysis demonstrated that only Caspase-8 was the independent variable affecting lung cancer BM. Elevated Caspase-8 predicted early metastasis to brain (Log Rank test, P=0.00). Our results suggest that elevated Caspase-8 was associated with increased incidence of brain metastasis after surgery in NSCLC patients, further evaluation of Caspase-8 as a biomarker for identification of patients at high risk of brain metastasis is warranted.