Elevated expression of phospho-acetyl-CoA carboxylase protein is an independent prognostic factor for human gastric cancer without lymph node metastasis
Background As a rate-limiting enzyme of fatty acid synthesis, acetyl-CoA carhoxylases (ACC) up-regulation has been recognized in multiple human cancers, implicating a critical role in cancer development and progression, yet its role in gastric cancer still remains unclear.In present study, we detected ACC and pACC expression in gastric cancers and explored its clinical significance.Methods Tissue microarray blocks containing primary gastric cancer and adjacent normal mucosa specimens obtained from 1,072 Chinese patients were used for the detection of ACC and pACC expression by immunohistochemistry.Gastric cancer cell lines were treated by metformin and pACC was measured by Western blotting.Results ACC overexpression was observed in all the tumor specimens.High expression of pACC was found in 630 (58.8%) of the 1,072 primary tumors and in 237 (66.6%) of the 356 primary tumors without lymph node metastasis, Absent/low expression of pACC significantly correlated with advanced T stage, tumor size, lymph node metastasis, advanced disease stage, and poor histological differentiation in 1,072 primary tumors, and with advanced T stage, tumor size, and poor histological differentiation in 356 tumors without lymph node metastasis.Kaplan-meier analysis showed that high expression of pACC is strongly related with better survival rates in all gastric cancer patients.Cox regression analysis revealed that pACC is an independent prognostic factor only in patients without lymph node metastasis.Metformin treatment leaded to increased expression of pACC, which, in turn, resulted in the reduction of cell proliferation and colony formation of gastric cancer cells.Conclusions Increased activation of ACC is frequent in human gastric cancer and downregulation of pACC is an important prognostic factor, suggesting that ACC/pACC might be a potential target for cancer intervention.
Gastric Carcinoma ACC pACC Prognosis Metformin Immunohistochemistry
Wenzhang Fang Guanzhen Yu Jiejun Wang
Department of Medical Oncology,Changzheng Hospital,Shanghai,People” s Republic of China
国内会议
上海
英文
26-32
2014-06-21（万方平台首次上网日期，不代表论文的发表时间）