Expression And Significance Of Fibroblast Activation Protein-α In Non-small Cell Lung Cancer And Association With Lymphocytes Ratio In Peripheral Blood Leukocytes

Background:Substantial clinical evidence suggested that lymph node metastasis plays an important role in lung cancer prognosis, but it is still unclear how a lymph node metastasis can happen. Lymph node is an important organ in immunological response. Thus raises the hypothesis that changes of immunity system components may associate with lymph node metastasis. Immunity suppression plays an important role in tumor progression, to date, researchers have found lots of mechanisms may be involved in this process. Recent animal experiment suggested that FAP-a had immunity suppression function, whether it has such effect in vivo and how can it induce this effect is still unclear. We hypothesis that FAP-a expression may involved in the change of lymphocytes ratio in peripheral blood leukocytes (L Y%) in non-small cell lung cancer (NSCLC).Methods:We performed a retrospective study of239patients who received surgery after the diagnosis in2008. To evaluate associations between lymphocytes ratio in peripheral blood leukocytes (LY%) and lymph node metastasis, COX regression analysis was applied to find the influenced parameters to survival, and Kaplan-Meier analysis was used for survival comparison. We collected patients tissue specimens surgically removed paraffin embedded tissues in Provincial Hospital. All tissue specimens of different groups were stained with a polyclonal antibody to FAP-a according to standardized immunohistochemistry method, so as to evaluate association between lymphocytes ratio in peripheral blood leukocytes (LY%) and FAP-a expression.Results:Two variables were independent predictors of survival:lymph node metastasis (LN) and LY%. According to LY%, the population could be divided into three subgroups:Decreased LY%, Normal LY%and Increased LY%. Decreased LY%significantly associated with the mortality rate compared to Increased LY%group. There was a significant difference existing in lymph node metastasis rate between Decreased LY%and Increased LY%groups, Decreased LY%and Normal LY%groups. Two variables were independent predictors of survival:N stage (P=0.02) and FAP-α expression level (P=0.03). According to LY%, the population could be divided into three subgroups:decreased, normal and increased. FAP-α expression level in three groups had a significantly difference (F=3.52, P=0.04, ANOVA analysis). High expression level of FAP-α significantly correlates decreased LY%(r=-0.32P=0.01). Higher FAP-α expression associated with poor prognosis (log-rank test:χ2=3.85P=0.05).Conclusions:Decreased LY%strongly correlates with lung cancer lymph node metastasis and survival. High expression of Fibroblast activation protein-α (FAP-α) associates with decreased lymphocytes ratio in peripheral leukocytes and predicts poor prognosis in NSCLC.