The expression of beclin-1, an autophagic gene, in hepatocellular carcinoma associated with clinical pathological and prognostic significance

BMC Cancer

Dong-Mei Qiu¹  Gui-Lan Wang¹  Li Chen¹  Yu-Yin Xu¹  Song He²  Xiao-Lei Cao¹  Jing Qin¹  Jia-Ming Zhou¹  Yi-Xin Zhang²  Qun E¹ 

[1] Department of Pathological Anatomy, Nantong University, Qixiu road 19#, Nantong, Jiangsu Province, China 226001

[2] Nantong Tumor Hospital, Nantong, P.R. China

关键词: Microvessels;    Prognosis proliferation, Apoptosis;    HCC;    Autophagy;    Beclin-1;   

Others  :  858831
DOI  :  10.1186/1471-2407-14-327

 received in 2014-01-18, accepted in 2014-04-28,  发布年份 2014

【 摘 要 】

Background

A role for autophagy, a conserved cellular response to stress, has recently been demonstrated in human cancers. Aberrant expression of Beclin-1, an important autophagic gene, has been reported in various human cancers. In the present study, we investigated the significance and relationship between Beclin-1 expression and cell proliferation, apoptosis, microvessel density (MVD) and clinical pathological changes or prognosis in human hepatocellular carcinoma (HCC).

Methods

A total of 103 primary HCC patients were involved in the study. Expression of Beclin-1, PCNA, NET-1, Bcl-2, Bax, Survivin in cancer cells and CD34 in stromal microvessels were evaluated immunohistochemically in tissue microarrays comprising 103 cases of HCC and 57 matched adjacent nontumor liver tissues. Correlations between clinicopathological characteristics and survival of HCC patients were explored.

Results

The positive rate of Beclin-1 was significantly lower in HCC tissues than adjacent tissues (72.8 vs. 89.5%, χ2 = 6.085, P = 0.015). In HCC, Beclin-1 expression was negatively correlated with cirrhosis background (r = −0.216, P = 0.029), Edmondson grade (r = −0.249, P = 0.011), vascular invasion (r = −0.246, P = 0.012), PCNA (r = −0.242, P = 0.014), NET-1 (r = −0.245, P = 0.013), anti-apoptosis protein Bcl-2 (r = −0.245, P = 0.013) and MVD (r = −0.292, P = 0.003), and positively correlated with pro-apoptosis protein Bax (r = 0.242, P = 0.014).

Significant differences in the 5-year survival rates were seen among patients with Beclin-1 strong positive (++) (59.1%, 13/22), moderate positive (+) (28.3%, 15/53) and weak negative expression (−) (14.6%, 7/28) (P = 0.043). Significant differences were detected between Beclin-1 (++) and either Beclin-1 (+) (P = 0.036) or Beclin-1 (−) groups (P = 0.008), but no significant difference between Beclin-1 (+) and Beclin-1 (−) groups (P = 0.281) was observed.

Survival rates were positively related to high Beclin-1 co-expressed with low PCNA, NET-1, or Bcl-2, lower MVD, and high Bax. Univariate and multivariate Cox regression analysis revealed that Beclin-1 expression was an independent indicator for overall survival in HCC patients (P < 0.05).

Conclusions

The pathogenesis and progression of HCC are associated with reduced autophagy. The expression of Beclin-1 and Bax in HCC tissues may provide a synergistic effect towards inhibiting HCC proliferation, infiltration, metastasis and angiogenesis. Beclin-1 expression may be a valuable prognostic marker of HCC.

【 授权许可】

   
2014 Qiu et al.; licensee BioMed Central Ltd.

【 图 表 】

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