Beclin 1 expression is an independent prognostic factor for gastric carcinomas.

Abstract

Beclin 1, an important autophagy-related protein in human cells, is involved in autophagy, differentiation, anti-apoptosis, and cancer progression, which is increased during periods of cell stress and extinguished during the cell cycle. In order to clarify the role of Beclin 1 in gastric carcinogenesis and subsequent progression, its expression was examined by immunohistochemistry and in situ hybridization (ISH) on tissue microarrays containing gastric carcinomas, adjacent non-neoplastic mucosa, and metastatic lymph node. Gastric carcinoma tissue and cell lines were studied for Beclin 1 expression by Western blot or RT-PCR, respectively. The results demonstrated that Beclin 1 was distinctively expressed in GES-1, AGS, BGC-823, GT-3 TKB, HGC-27, KATO-III, MGC-803, MKN28, MKN45, SCH, SGC-7901, or STKM-2 at both mRNA and protein levels. However, Beclin 1 mRNA was highly expressed in gastric carcinoma than matched mucosa by real-time PCR and ISH (P < 0.05). Beclin 1 expression was negatively related to distant metastasis and poor prognosis of gastric carcinoma (P < 0.05). Beclin 1 was highly expressed in male than female patients with gastric carcinoma (P < 0.05). The 65-year-elder patients with gastric carcinoma had higher Beclin 1 expression than the younger ones (P < 0.05). The diffuse-type carcinomas showed less Beclin 1 expression than intestinal- and mixed-type ones (P < 0.05). In intestinal-type gastric carcinoma, Beclin 1 expression was inversely associated with venous invasion, lymph node metastasis, and tumor-node-metastasis (TNM) staging (P < 0.05). Kaplan-Meier analysis indicated that Beclin 1 expression was positively linked to favorable prognosis of the patients with overall and intestinal-type carcinoma (P < 0.05). Cox's proportional hazard model indicated that venous invasion, lymph node metastasis, distant metastasis, TNM staging, and Beclin 1 expression were independent prognostic factors for gastric carcinomas (P < 0.05). It was suggested that aberrant Beclin 1 expression is closely linked to pathogenesis, metastasis, and differentiation of gastric carcinoma. Beclin 1 expression might be employed to indicate the favorable prognosis of gastric carcinomas as an independent factor.

• Authors: Miao Yu, Wen-feng Gou, Shuang Zhao, Li-jun Xiao, Xiao-yun Mao, Ya-nan Xing, Hiroyuki Takahashi, Yasuo Takano, Hua-chuan Zheng
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 34 Issue 2 Pg. 1071-83 (Apr 2013) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 23334926 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• BECN1 protein, human
• Beclin-1
• Biomarkers, Tumor
• Membrane Proteins
• RNA, Messenger

Topics

• Adenocarcinoma (metabolism, mortality, pathology)
• Adult
• Aged
• Aged, 80 and over
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Beclin-1
• Biomarkers, Tumor (genetics, metabolism)
• Blotting, Western
• Disease Progression
• Female
• Fluorescent Antibody Technique
• Follow-Up Studies
• Humans
• Immunoenzyme Techniques
• In Situ Hybridization
• Lymphatic Metastasis
• Male
• Membrane Proteins (genetics, metabolism)
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Staging
• Prognosis
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Stomach Neoplasms (metabolism, mortality, pathology)
• Survival Rate
• Tissue Array Analysis
• Tumor Cells, Cultured