Expression Of VEGF-VEGFR In Human Small Bowel Adenocarcinoma And Effects Of VEGFR-2 Inhibitor In Vivo

Objective: Small bowel adenocarcinoma is a rare gastrointestinal malignant tumor.Because of its atypical early symptoms,clinical diagnosis is difficult and prognosis is poor.There are few clinical studies on its biological characteristics,diagnostic and therapeutic methods and prognosis.The VEGF-VEGFR protein family is closely related to tumorigenesis and development.A large number of experiments have proved that VEGF-VEGFR is closely related to neovascularization,lymphatic metastasis and TNM stage of tumors.VEGFR-2 antagonists are widely used in clinic,and their effects are definite.A large number of clinical studies have confirmed that they can significantly improve patients OS and PFS.However,there are few studies on the expression of VEGF-VEGFR in small bowel adenocarcinoma and its relationship with the biological characteristics.The clinical application of the VEGFR-2 in small bowel adenocarcinoma has not been reported yet.In order to provide more experimental and clinical evidences for the treatment of small bowel adenocarcinoma,this paper investigated the significance of expression of VEGF-VEGFR in small bowel adenocarcinoma and the clinical application of VEGFR-2 antagonist in small bowel adenocarcinoma.Methods : 1.From January 2010 to March 2017,this paper collected 87 patients with primary small bowel adenocarcinoma diagnosed and treated by surgery in Sichuan Province People's Hospital which have complete clinical and pathological data.Immunohistochemistry was used to detect the expression of VEGF-A,VEGF-B,VEGFR-1,VEGFR-2 and VEGFR-3 in tumor tissues.The results were correlated with the clinicopathological characteristics of patients.2.Four patients with primary small bowel adenocarcinoma treated with VEGFR-2 antagonist in the Department of gastrointestinal surgery of Sichuan People's Hospital from September 2017 to May 2018.The therapeutic effects and adverse reactions were analyzed.Results: 1.A total of 87 patients with small bowel adenocarcinoma were enrolled.The patients' gender and age played no statistical significance in the expression of VEGF-A,VEGF-B,VEGFR-1,VEGFR-2 and VEGFR-3 in small bowel adenocarcinoma tissues(P > 0.05).The expression of VEGFR-1 in duodenum was higher than that in jejunum and ileum,the difference has statistically significant(P = 0.003).The difference between VEGF-B,VEGFR-1,and VEGFR-2 expression and tumor histological grades has statistically significant(P =0.045,0.005 and 0.034).In the depth of invasion staging of tumors,the expressions of VEGF-A and VEGFR-1 were stronger in patients with higher T staging,and the difference was statistically significant(P < 0.000).The positive rates of expression VEGFR-2 and VEGFR-3 in tumors with lymph node metastasis were higher than those without lymph node metastasis(P < 0.000).The expression of VEGF-A and VEGF-B was different in different TNM stages.The positive expression rate of VEGF-A and VEGF-B in patients with stage ? was higher than that in patients with stage ? and stage ?/?,and there was a positive correlation among them(all P < 0.000).2.Among the four patients,three were female and one was male,the ratio of male to female was 3: 1.The average age of operation was 55.3 � 24.4(49-62)years old.One of them originated from duodenum,two from jejunum,one from ileum,and the TNM stage was ?.The overall survival time is 5 months,11 months,13 months and 14 months.Conclusion:1.Vascular endothelial cell membrane and diffuse expression of vascular endothelial cell were observed in the cytoplasm of small bowel cancer,and there was small amount expression on vascular endothelial cell membrane.The expression of VEGFR-1?VEGFR-2 and VEGFR-3 was mainly on vascular endothelial cell membrane and lymphatic endothelial cell membrane.2.At the protein level,the expression level of VEGFR-1 in different parts of small bowel adenocarcinoma is different,and the expression level of VEGFR-1 in duodenum is higher than that in jejunum and ileum.In different histological grades,the expression levels of VEGF-B,VEGFR-1 and VEGFR-2 are different,and the expression rate of the above-mentioned proteins with worse histological grade is higher.In the stage of invasion depth of tumors,the expression level of VEGF-A and VEGFR-1 is higher than that of jejunum and ileum.Patients with advanced T stage were higher.The expression of VEGF-2 and VEGFR-3 was higher in patients with lymph node metastasis.The expression of VEGF-A and VEGF-B was different in different TNM stages.The positive expression rate of VEGF-A and VEGF-B in patients with TNM stage ? was higher than that in patients with stage ? and stage ?/?.3.Among the four patients with small bowel adenocarcinoma,Apatinib combined with FORFIRI is effective and has controllable adverse reactions.However,large-scale randomized controlled trials are needed to further study its efficacy and safety.