| Background:Adenoid cystic carcinoma (ACC) mainly occurs in salivary tissues and is one of the most frequent malignant tumors of the salivary glands in the head and neck. Adenoid cystic carcinoma has three types of pathological patterns, including tubular, cribriform and solid. It is difficult to grade this tumor because there are usually two kinds of types in the tumor. Clinically, a solid pattern indicates a poor prognosis. Adenoid cystic carcinoma usually grows slowly and it is rare to detect the lymph node transferring. However, it is described as one of the most destroyed and unpredicted malignant tumors because its propensity of perineural invasionPreliminary studies of our group have confirmed that autophagy related gene expression is closely related with the occurrence and development of the ACC. Autophagy is a process whereby cell components are captured within autophagosomes, and are delivered to the lysosomes for degradation. Autophagy facilitates cellular survival by maintaining energy homeostasis and macromolecular synthesis during cellular stress and nutrient deprivation. Recent studies show that hypoxia could induce autophagy and HIF-la/BNIP3 pathway plays a vital role in hypoxia-induced autophagy. However, the expression of BNIP3 and genes related with hypoxia-induced autophagy is unexplored in adenoid cystic carcinoma. And we also lack the knowledge about BNIP3’s relationship with the clinicopathological features in the adenoid cystic carcinoma. And further investigations are needed foe the role of BNIP3 in the hypoxia-induced autophagy.In our study, we investigated the expression of BNIP3, HIF-1α and LC3 by immunohistochemical analysis in head and neck salivary adenoid cystic carcinoma and normal salivary tissue. We also correlated BNIP3, HIF-la and LC3 expression with histopathogic prognostic factors and survival. Additionally, we observed the expression of BNIP3, HIF-1α and LC3 in ACC-M cells under hypoxic condition.OBJECTIVE:This study investigated expression of BNIP3 in ACC tissues and cells and elucidated its correlations to clinicopathological features in ACC. And the study also explores the role of BNIP3 in hypoxia-induced autophagy.METHODS:Immunohistochemical and immunofluorescence staining were used to explore BNIP3, HIF-1α and LC3 expression and their expression levels are analyzed in terms of age, gender, clinical stage, tumor size, pathological grade and distant metasis. The survival rate are analyzed by Kaplan-Meier.ACC-M cells are cultivated under hypoxic condition induced by cobalt chloride. Immunofluorescence analyses are done to detect the expression of BNIP3, HIF-1α and LC3 in ACC-M cells.RESULTS:(1) BNIP3 was positively expressed in 41 cases (63.1%), and was significantly correlated with histological grade (P=0.001). HIF-1α was positively expressed in 52 cases (80.0%) and was significantly correlated with TNM stage (P=0.023) and histological grade (P=0.024). LC3 was positively expressed in 37 cases (56.9%) and was significantly correlated with TNM stage (P=0.019).(2) The expression of BNIP3 was correlated with HIF-la expression (P=0.011). on the contrary, the expression of BNIP3 was not significantly related with LC3 expression(3) The overall survival in the negative BNIP3 expression group tended to be better than in the positive BNIP3 expression (P=0.011), while there were no differences in the survival rate between HIF-la negative groups and positive group.(4) In vitro experiment, BNIP3 immunofluorescence staining was detected in cells treated with CoCl2 (for hypoxic condition). HIF-1α and LC3 were also detected in ACC-M cells.CONCLUSIONS:The data indicats that BNIP3 plays a vital role in the tumorigenesis of adenoid cystic carcinoma and might be a prognosis factor of the aenoid cystic carcinoma, which could provide a new direction for the therapy of adenoid cystic carcinoma. However, the role of BNIP3 in the hypoxia-induced autophagy is still unclear. |
PDF Full Text Request