| Objective:The objective of the present study was to detect the expression of Fascin in hunman early-stage non-small cell lung cancer(NSCLC) and paracarcinoma tissues, and explore the relevance between Fascin level and clinical pathological characteristics. Then we investigated the correlation between Fascin level and prognosis of early-stage NSCLC patients. Furthermore Fascin content was detected in the serum of early-stage NSCLC patients and normal control group, and the relationship between Fascin expression and the clinicopathological characteristics was analyzed. At last we evaluated the possibility of Fascin to provide predictable survival factor for postoperative NSCLC patients to improve the quality of NSCLC patients' life and prolong their survival period. Methods:Early-stage NSCLC tumor tissues were obtained from 111 patients who were diagnosed pathologically and underwent complete surgical resection at The Beijing Chest Hospital from January 2012 to December 2013, and preoperative serum samples in this study were collected consecutively from 78 cases of early-stage NSCLC patients and 42 healthy volunteers,serving as age-matched normal controls, by the staff of The Beijing Chest Hospital Sample Bank from August 2014 to March 2016. The complete clinical pathological datas, such as age, sex, smoking history, differentiation, pathological types, TNM stage, tumor size, lymph node metastasis and follow-up informations were collected. The immunohistochemistry method(Max Vision HRP-Polymer anti-Mouse/Rabbit IHC Kit) was used to assess the level of Fascin in stage I and stage II NSCLC formalin-fixed and paraffin-embedded(FFPE) tissues and paracarcinoma tissues. The expression of Fascin in vascular endothelial cells served as the positive control, and the primary antibody was replaced with phosphate buffered saline, which was used as the negative control. The results of Fascin detection were evaluated by immuneoreactivescore(IES). The serum Fascin content in early-stage NSCLC patients and healthy volunteers was determined using a quantitative sandwich enzyme-linked immunesorbent assay(Enzyme-linked lmmunosorbent Assay Kit For Fascin). The cut-off level of serum Fascin was defined as the mean+2standard deviations of the healthy. Associations of Fascin expression in early-stage NSCLC tissues and clinical pathological parameters were evaluated by ?2 test(applying Yates' correction for continuity). The relationships between the content of serum Fascin and the clinical pathological parameters were compared by two-sample t-test for independent samples and analysis of variance(ANOVA). The Kaplan–Meier method was employed for the survival analysis. In this study, the main outcome measures were DFS. The comparative importance of explanatory variables on survival time were evaluated by means of Cox's proportional hazard regression model.The statistical analysis was conducted in SPSS 19.0 statistical software(IBM SPSS, Chicago, IL, USA). Values of P<0.05 were considered statistically significant. Results:(1) Immunohistochemical results showed that Fascin was mainly localized in the cytoplasm and cell membrane of tumor cells. In 111 cases early-stage of NSCLC tissues, the positive rate of Fascin expression was 64.8%(72/111), no Fascin expression in the paracarcinoma tissue. The positive rate of squamous cell carcinoma was 78.7%(48/61), which was significantly higher that in adenocarcinoma 48.0%(24/50)(P=0.001).The serum Fascin level in early-stage NSCLC patients was significantly higher that in the control group[(2.355±1.741)vs( 1.6445±1.353) ng/ml, P=0.031]. The positive rate of serum Fascin was 16.7%(13/78)in early-stage NSCLC patients, which was obviously higher than that in healthy volunteers 3.1%(1/32)(P=0.043).(2) In the early-stage of NSCLC, the positive rate of Fascin was positively associated with clinical stage(I vs. II, P < 0.001) and N classification(N0 vs. N1, P = 0.001). However, there was no any significant association of Fascin level with patient's gender(male vs. female, P=0.179), age(<60 vs. ?60, P=0.651), smoking history(no vs. yes, P=0.103), and T classification(T1 vs. T2, P = 0.931). Fascin positive rate of stage I and II NSCLC tissues was 83.3%(50/60) and 43.1%(22/51), N1 and N0 NSCLC tissues was 86.4%(38/44) and 50.7%(34/67) respectively.The content of serum Fascin had no significant differences among early-stage NSCLC patients at different TNM stage(I vs. II, P=0.453) or N classification(N0 vs. N1, P=0.324). And no statistical significance was observed in the association of Fascin level with patient's gender(male vs. female, P=0.245), age(<60 vs. ?60, P=0.267), smoking history(no vs. yes, P=0.294), pathology classification(squamous cell carcinoma vs. adenocarcinoma, P=0.874), or T classification(T1 vs. T2, P =0.361).(3) In early-stage NSCLC tissues, Fascin level was correlated with the prognosis of early-stage NSCLC patients. Results of ?2 test showed that Fascin positive rate of the patients with recurrence and metastasis was 90.0%(36/40),the patients without tumor was 50.7%(36/71)(P<0.001).Based on Kaplan –Meier curves, patients with strong positive expression of Fascin had shorter DFS than thoes with weak positive Fascin expression(P=0.007),who had shorter DFS than thoes with negative Fascin expression(P<0.001).Univariate analyses revealed that lymph node metastasis, TNM stage, and Fascin expression status were correlated with poor DFS. According to the results of the regression analysis, high expression of Fascin was an independent prognostic factor for shorter DFS in patients with NSCLC.DFS analysis showed no significant differences between the positive and negative serum fascin groups among those patients by ?2 test and Kaplan–Meier curves(P=0.051,P= 0.163). Conclusion:(1) In early-stage NSCLC tissues, Fascin was abnormal high expressed,which was positively correlated with clinical TNM stage and N classification. It suggested that Fascin played an important role on early-stage NSCLC progression. The expression level of serum Fascin was significantly higher in early-stage NSCLC patients, but the high Fascin level was not correlated with TNM stage or N classification, which may meaned the serum level of Fascin protein was slightly correlated with the progression of early-stage NSCLC invasion.(2) Higher Fascin expression of early-stage NSCLC tissues was significantly associated with poor DFS in patients with early-stage NSCLC, and increased Fascin expression was possible to be a poor independent prognostic biomarker for NSCLC patients. However, the high serum Fascin level was not correlated with with NSCLC patients' DFS.It indicated that Fascin probably served as a convictive prognostic biomarker for NSCLC patients, but the potential value of serum Fascin in the evaluation of the NSCLC patients' prognosis still needed further research and evaluation. |
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