Beclin 1 expression is an independent prognostic factor for gastric carcinomas |
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Authors: | Miao Yu Wen-feng Gou Shuang Zhao Li-jun Xiao Xiao-yun Mao Ya-nan Xing Hiroyuki Takahashi Yasuo Takano Hua-chuan Zheng |
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Affiliation: | 1. Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China 2. Department of Biochemistry and Molecular Biology, Institute of Pathology and Pathophysiology, College of Basic Medicine, China Medical University, Shenyang, 110001, China 3. Department of Immunology, School of Basic Medicine, Chengde Medical Collge, Chengde, 067000, China 4. Clinical Research Institute, Kanagawa Cancer Center, Yokohama, 241-0815, Japan
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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. |
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