Nestin predicts a favorable prognosis in early ampullary adenocarcinoma and functions as a promoter of metastasis in advanced cancer

研究成果: Article同行評審

7 引文 斯高帕斯(Scopus)

摘要

Nestin exhibits stemness characteristics and is over-expressed in several types of cancers. Downstream signaling of nestin [cyclin-dependent kinase 5 (CDK5) and Ras-related C3 botulinum toxin substrate 1 (Rac1)] functions in cancer to modulate cellular behaviors. We studied the function of nestin in ampullary adenocarcinoma. Immunohistochemistry (IHC), reverse transcription-polymerase chain reaction, and cDNA microarray of nestin in ampullary adenocarcinoma was compared with normal duodenum. CDK5 and Rac1 were assessed by western blotting. We hypothesized that nestin/CDK5/Rac1 signaling behaves different in early and advanced cancer. We found that the presence of nestin mRNA was increased in the early stages of cancer (T2N0 or T3N0) and advanced cancer with lymph node metastasis (T4N1). A total of 102 patients were enrolled in the IHC staining. Weak nestin expression was correlated with favorable characteristics of cancer, decreased incidence of local recurrence and lower risk of recurrence within 12 months after surgery. Patients with weak nestin expression had the most favorable recurrence-free survival rates. Patients with mild to strong nestin expression exhibited an advanced behavior of cancer and increased possibility of cancer recurrence. The reciprocal expression of nestin and RAC1 were explored using a cDNA microarray analysis in the early stages of ampullary adenocarcinoma. Increased level of CDK5 with simultaneously decreased expression of Rac1 was detected by western blotting of ampullary adenocarcinoma in patients without cancer recurrence. The activation of multiple oncogenic pathways, combined with the stemness characteristics of nestin, formed a complex network in advanced ampullary adenocarcinoma. Our study demonstrated that nestin performs a dual role in ampullary adenocarcinoma. Appropriate amount of nestin enhances CDK5 function to suppress Rac1 and excessive nestin/CDK5 participates in multiple oncogenic pathways to promote cancer invasiveness. Inhibiting nestin in patients who exhibit nestin-overexpressed ampullary adenocarcinoma may be a method of preventing cancer recurrence.

原文English
頁(從 - 到)40-48
頁數9
期刊Oncology Reports
33
發行號1
DOIs
出版狀態Published - 2015 一月 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

指紋 深入研究「Nestin predicts a favorable prognosis in early ampullary adenocarcinoma and functions as a promoter of metastasis in advanced cancer」主題。共同形成了獨特的指紋。

引用此