Loss of autophagy-related protein Beclin 1 may define poor prognosis in ovarian clear cell carcinomas

Katagiri,Hiroshi; Nakayama,Kentaro; Razia,Sultana; Nakamura,Kohei; Sato,Emi; Ishibashi,Tomoka; Ishikawa,Masako; Iida,Kouji; Ishikawa,Noriyoshi; Otsuki,Yoshiro; Nakayama,Satoru; Kyo,Satoru

doi:10.3892/ijo.2015.3191

Loss of autophagy-related protein Beclin 1 may define poor prognosis in ovarian clear cell carcinomas

Authors:
- Hiroshi Katagiri
- Kentaro Nakayama
- Sultana Razia
- Kohei Nakamura
- Emi Sato
- Tomoka Ishibashi
- Masako Ishikawa
- Kouji Iida
- Noriyoshi Ishikawa
- Yoshiro Otsuki
- Satoru Nakayama
- Satoru Kyo
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Affiliations: Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 693-8501, Japan, Department of Organ Pathology, Shimane University School of Medicine, Izumo 693-8501, Japan, Department of Pathology, Seirei Hamamatsu General Hospital, Hamamatsu 430-8558, Japan, Department of Obstetrics and Gynecology, Seirei Hamamatsu General Hospital, Hamamatsu 430-8558, Japan
Published online on: October 6, 2015 https://doi.org/10.3892/ijo.2015.3191
Pages: 2037-2044
Copyright: © Katagiri et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to clarify the role of autophagy in cisplatin (CDDP) sensitivity in OCCCs and the role of Beclin 1 in OCCC progression. Autophagy was measured using: i) western blot analysis of LC3 and p62 and ii) microscopic observation of GFP-LC3 puncta. Autophagy was suppressed using chloroquine and Beclin 1 siRNA. Surgical specimens were examined for Beclin 1 protein expression by immunohistochemistry. The correlations between the loss of Beclin 1 expression and clinicopathological characteristics, prognosis and chemosensitivity were investigated. Inhibition of autophagy by chloroquine or Beclin 1 siRNA did not enhance the sensitivity of the ES2 and TOV-21G OCCC cell lines to CDDP. Loss of Beclin 1 expression was observed in 38.3% (23/60) of the analyzed tumors. There was no significant correlation between loss of Beclin 1 expression and FIGO stage, CA125 levels, patient age, status of endometriosis, Ki-67 labeling index, chemotherapy regimen or status of residual tumor. However, negative expression of Beclin 1 was associated with a shorter progression-free survival in comparison to positive Beclin 1 expression in OCCC who received cytoreductive surgery, followed by a standard platinum-based chemotherapy regimen (P=0.027, log-rank test). Beclin 1-negative tumors were no more resistant to primary adjuvant chemotherapy than were Beclin 1-positive tumors (50.0 vs. 66.7%, P=0.937). Beclin 1 knockdown using siRNA increased cell growth but not cell migration and invasion in ES2 and TOV-21G OCCC cell lines. Autophagy defects caused by loss of Beclin 1 are not related to chemoresistance and metastasis, but may be associated with malignant phenotype and poor prognosis of OCCC.

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