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Aberrant Beclin 1 expression is closely linked to carcinogenesis, differentiation, progression, and prognosis of ovarian epithelial carcinoma

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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 suppression, which is increased during periods of cell stress and extinguished during cell cycle. Human ovarian tumors display allelic loss of Beclin 1 with high frequency. To clarify Beclin 1's role in ovarian carcinogenesis and subsequent progression, its expression was examined by immunostaining on tissue microarrays containing ovarian normal tissue, benign and borderline tumors, and carcinomas. Beclin 1 mRNA and protein expression was examined in ovarian normal tissue, benign and borderline tumors, carcinoma tissue, and cell lines by reverse transcription polymerase chain reaction or Western blot, respectively. The results demonstrated that the higher Beclin 1 mRNA was observed in ovarian benign tumor than normal ovary and ovarian carcinoma (P < 0.05) and negatively correlated with the differentiation of ovarian carcinoma (P < 0.05). Beclin 1 protein expression was stronger in ovarian carcinoma than that in normal ovary and inversely related to the differentiation of ovarian carcinoma (P < 0.05) by Western blot. Immunohistochemically, Beclin 1 expression was statistically higher in ovarian borderline tumor and carcinoma than normal ovary and benign tumor (P < 0.05) and inversely linked to differentiation, lower ki-67 expression, and higher cumulative or relapse-free survival rate of ovarian carcinoma (P < 0.05). Cox proportional hazard model indicated that age and International Federation of Gynecology and Obstetrics staging (P < 0.05), but not pathological classification differentiation degree or Beclin 1 expression, were independent prognostic factors for overall and relapse-free ovarian carcinomas (P > 0.05). It was suggested that the aberrant Beclin 1 expression is closely linked to tumorigenesis and differentiation of ovarian carcinoma. Beclin 1 expression might be employed to indicate the worse prognosis of ovarian carcinomas, albeit not 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), Project Supported by Scientific Research Fund of Liaoning Provincial Education Department (L2010633), Liaoning Science and Technology Grant (2009225008-11), Natural Scientific Foundation of China (nos. 81172371 and 81202049), 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 Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China

    Yang Zhao & Shuo Chen

  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, Li-jun Xiao & Hua-chuan Zheng

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

    Yasuo Takano

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  1. Yang Zhao
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  2. Shuo Chen
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  3. Wen-feng Gou
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  6. Hua-chuan Zheng
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Correspondence to Hua-chuan Zheng.

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Zhao, Y., Chen, S., Gou, Wf. et al. Aberrant Beclin 1 expression is closely linked to carcinogenesis, differentiation, progression, and prognosis of ovarian epithelial carcinoma. Tumor Biol. 35, 1955–1964 (2014). https://doi.org/10.1007/s13277-013-1261-6

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  • DOI: https://doi.org/10.1007/s13277-013-1261-6

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