Relationship And Prognostic Significance Of SPARC And VEGF Protein Expression In Colon Cancer

Objective:Colon carcinoma is the common cancer of digestive tract,can occur in any part of the colon,and is the fifth～sixth of total mortality in China.To improve the survival rate of colon carcinoma patients,assess the prognosis of patients from molecular biology level and detection effectively target of molecular targeted therapy drugs is particularly important,and to block the signal transduction pathway and the key target molecule of tumor has become the hot spots for the treatment of colon carcinoma.Whether the signaling pathway and target molecule is closely related to the occurrence of colon cancer is the precise molecular basis for targeted therapy.Recent studies have found that SPARC(secreted protein,acidic and rich in cysteine)is closely related with the progress,invasion and metastasis of malignant tumor.This study investigates the relationship between SPARC and vascular endothelial growth factor(VEGF),and as well as their prognostic significance in patients with human colon adenocarcinoma tissues,and to provide another theoretical basis for the molecular targeted therapy of colon carcinoma.Methods:Immunohistochemical staining was used to determine protein expression of SPARC,vascular endothelial growth factor(VEGF),in a set of 114 formalinfixed, paraffin-embedded primary colon adenocarcinoma(hereinafter referred to as colon cancer)and its match the normal mucosal tissues away from the tumor tissue. Evaluation of VEGF in the same tissue established the antigenic profiles,while CD34 was used as an indicator ofmicrovessel density(MVD).Results:(1)SPARC expression was mainly in the stromal cells surrounding the colon adenocarcinoma,it was no significant difference between cancer cells and normal mucosa tissue(P=0.657),but there were significant differences betweem stromal cells surrounding malignant tissues and normal mucosal tissue and cancer cells with SPARC expression(respectively,P=0.002,P=0.006);the positive expression rate of VEGF in colon adenocarcinoma and normal mucosa tissue was 72.8%and 47.4%respectively,it was significant difference between them(P=0.001); CD34 was the marker of vascular endothelial cells,MVD mean value was 11.60±5.68 in all colon adenocarcinoma,the microvessel density within tumor tissue was significantly higher than the surrounding normal tissue.(2)Expression of SPARC in the tumor stromal cells was significant difference with the differentiation degree of tumor and lymph node metastasis(respectively P=0.046,P=0.013),and was negative related with the differentiation degree of tumor (P＜0.05,r=-0.175),but there were no difference with Patient age,sex,tumor size, tumor location,lymphatic infiltration,depth of invasion and TNM staging(P＞0.05);it was significant difference with VEGF expression between lymph node metastasis and TNM staging(respectively P=0.001,P=0.002),and was positive related with TNM staging(P＜0.05,r=0.302).(3)Expression of SPARC was also significantly correlated with VEGF(r=-0.208, P=0.001),and MVD(r=-0.578,P=0.001)in colon adenocarcinoma tissues.(4)Patients low rexpressing SPARC had significantly worse overall(P=0.006)and disease-free survival(P=0.012)in a Single factor analysis and log-rank test;VEGF in patients with high expression were worse overall(P=0.003)and disease-free survival (P=0.001)than patients with low expression.(5)When SPARC,differentiation degree,lymphatic metastasis,lymphocytic infiltration,invasion depth,distant metastasis,TNM staging,and the levels of VEGF, MVD were included in a multivariate Cox regression analysis,SPARC emerged as an OS independent prognostic factor for colon adenocarcinoma(P=0.006),along with VEGF(P=0.042)and TNM staging(P=0.008),SPARC is also affected DFS in patients with an independent prognostic factor(P=0.030).Conclusion:These results suggest that the low or absence SPARC expression was closely related with the differentiation degree of tumor and lymph node metastasis,it was an independent prognostic factor for poor prognosis of colon adenocarcinoma. SPARC expression had significant correlation with angiogenic factors VEGF,and may be involved in the role of anti-angiogenesis,and the molecular regulation mechanism may become a new way for treatment of the tumor and will be a meaningful reference for molecular target therapy of colon cancer.