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Beclin 1 expression is an independent prognostic factor for gastric carcinomas

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Tumor Biology

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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Acknowledgments

This study was supported by the Shenyang Outstanding Talent Foundation of China, Shenyang Science and Technology Grant (F11-264-1-10, F12-277-1-01), Natural Scientific Foundation of China (81201886, 81101886, 81172371, and 81101885), Liaoning Science and Technology Grant (2011225019), and Grant-in aid for Scientific Research from the Ministry of Education, Culture, Sports and Technology of Japan (23659958).

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Authors and Affiliations

  1. Department of Surgical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China

    Miao Yu, Xiao-yun Mao & Ya-nan Xing

  2. Department of Biochemistry and Molecular Biology, Institute of Pathology and Pathophysiology, College of Basic Medicine, China Medical University, Shenyang, 110001, China

    Wen-feng Gou & Hua-chuan Zheng

  3. Department of Immunology, School of Basic Medicine, Chengde Medical Collge, Chengde, 067000, China

    Shuang Zhao & Li-jun Xiao

  4. Clinical Research Institute, Kanagawa Cancer Center, Yokohama, 241-0815, Japan

    Hiroyuki Takahashi & Yasuo Takano

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  1. Miao Yu
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Correspondence to Hua-chuan Zheng.

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Yu, M., Gou, Wf., Zhao, S. et al. Beclin 1 expression is an independent prognostic factor for gastric carcinomas. Tumor Biol. 34, 1071–1083 (2013). https://doi.org/10.1007/s13277-013-0648-8

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  • DOI: https://doi.org/10.1007/s13277-013-0648-8

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