Mechanism of Beclin1 as a favorable molecules marker is that Beclin1 inhibits tumor proliferation and cell cycle arrest in stage IIIB colon cancers

Abstract

Objective Beclin1 is a multi-function protein，bridging autophagy，apoptosis and differentiation. Our previous study found that Beclin1 was a favorable prognostic biomarker in locally advanced colon carcinomas. This study investigated the expression of Beclin1 in human colon cancers and its mechanism as a favorable molecules marker. Methods A total of 104 cases of colon cancer specimens and clinical data were obtained from Chinese stage ⅢB colon cancer patients with intact follow-up data who subjected to radical resection between Jan，1999 and July，2003 in the cancer center of Sun Yat-Sen University. The specimens were constructed from formalin-fixed，paraffin-embedded tissues. The expression of Beclin1 in primary tumors matched with adjacent noncancerous tissue were examined with immunohistochemistry technique. Additionally，immunofluorescence double staining technique was used to investigate the molecular mechanism by analyzing coexpression of the protein PCNA and Beclin1. Results The expression of Beclin1 was observed in plasma-membrane，cytoplasm and nucleus in tumor cells. In the tumor tissues analyzed，immunopositivity was observed for Beclin1 in 87(83.7% ) of the 104 tumor tissues. In contrast，adjacent non-cancerous tissues and normal tissues showed no or very weak expression of Beclin1. The 5-year overall survival rate for Beclin1 immunopositivity cases was 69.8%. Beclin1 immunonegativity was 47.1%. Both univariate analysis and multivariate analysis showed that Beclin1 and T stage were independent prognostic factors. The immunofluorescence double staining showed the expression of Beclin1 negatively correlated with the expression of PCNA，which indicates Beclin inhibits tumor proliferation and cell cycle arrest. Conclusions Beclin1 plays important roles in the regulation of the life span of human colon cells by inhibiting tumor proliferation and cell cycle arrest in stage ⅢB colon cancers. Beclin1 is a favorable prognostic biomarker in locally advanced colon carcinomas and provides the information regarding the likely targeted therapy intervention. In future，with the progress of autophagy analysis technique，it is critical to determine the autophagy pathway responsible for colon cancer in cell lines and animal models to define targets to fight the locally advanced colon cancer.