Association of BDNF and BMPR1A with clinicopathologic parameters in benign and malignant gallbladder lesions

World Journal of Surgical Oncology

Xiongying Miao²  Zhulin Yang¹  Yu Wen²  Xiaofeng Deng²  Li Xiong² 

[1] Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China;Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, PR China

关键词: Clinicopathology;    BMPR1A;    BDNF;    Gallbladder lesions;   

Others  :  825732
DOI  :  10.1186/1477-7819-11-80

 received in 2012-10-05, accepted in 2013-02-23,  发布年份 2013

【 摘 要 】

Background

Neurotrophic factors such as brain derived neurotrophic factor (BDNF) are synthesized in a variety of neural and non-neuronal cell types and regulate survival, proliferation and apoptosis. In addition, bone morphogenetic proteins (BMPs) inhibit the proliferation of pulmonary large carcinoma cells bone morphogenetic protein receptor, type IA (BMPR1A). Little is known about the expression of BDNF or BMPR1A in malignant gall bladder lesions. This study was to evaluate BDNF and BMPR1A expression and evaluate the clinicopathological significance in benign and malignant lesions of the gallbladder.

Methods

The BDNF and BMPR1A expression of gallbladder adenocarcinoma, peritumoral tissues, adenoma, polyp and chronic cholecystitis were Immunohistochemically determined.

Results

BDNF expression was significantly higher in gallbladder adenocarcinoma than in peritumoral tissues, adenoma, polyps and chronic cholecystitis samples. However, BMPR1A expression was significantly lower in gallbladder adenocarcinoma than in peritumoral tissues, adenomas, polyps and chronic cholecystitis tissues. The specimens with increased expression of BDNF in the benign lesions exhibited moderate- or severe-dysplasia of gallbladder epithelium. BDNF expression was significantly lower in well-differentiated adenocarcinomas with maximum tumor diameter <2 cm, no metastasis to lymph nodes, and no invasion of regional tissues compared to poorly-differentiated adenocarcinomas with maximal tumor diameter >2 cm, metastasis of lymph node, and invasiveness of regional tissues in gallbladder adenocarcinoma. BMPR1A expression were significantly higher in the well-differentiated adenocarcinoma with maximal tumor diameter <2 cm, no metastasis of lymph node, and no invasion of regional tissues compared to poorly-differentiated adenocarcinomas with maximal tumor diameter >2 cm, metastasis of lymph node, and invasiveness of regional tissues in gallbladder. Univariate Kaplan-Meier analysis indicated increased expression of BDNF or decreased expression of BMPR1A was associated with decreased disease specific survival (DSS) rates. Similarly, multivariate Cox regression analysis showed increased expression of BDNF or decreased expression of BMPR1A are independent predictors of poor DSS rates in gallbladder adenocarcinoma.

Conclusions

In gallbladder malignancies, the increased expression of BDNF and decreased expression of BMPR1A were associated with increased risk of metastasis, regional invasion and mortality. They might serve as novel indicators of gallbladder adenocarcinoma outcomes, which may prove valuable for the development of personalized therapeutic paradigms.

【 授权许可】

   
2013 Xiong et al.; licensee BioMed Central Ltd.

【 图 表 】

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