Loss of beclin 1 expression in ovarian cancer: A potential biomarker for predicting unfavorable outcomes

卵巢癌中 Beclin 1 表达缺失:预测不良结果的潜在生物标志物

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作者:Toshiko Minamoto, Kentaro Nakayama, Kohei Nakamura, Hiroshi Katagiri, Razia Sultana, Tomoka Ishibashi, Masako Ishikawa, Hitomi Yamashita, Kaori Sanuki, Kouji Iida, Satoru Nakayama, Yoshiro Otsuki, Noriyuki Ishikawa, Satoru Kyo

Abstract

The clinicopathological significance and prognostic value of the expression of proteins associated with autophagy, beclin 1 (BECN1), 1A/1B-light chain 3 (LC3) and high mobility group box-1 protein (HMGB-1), were investigated in patients with ovarian carcinoma, receiving combination chemotherapy with a platinum agent and a taxane. Immunohistochemical staining was performed for autophagy-associated proteins in tumor tissues from 141 patients with ovarian carcinoma. Clinical data were collected retrospectively by reviewing medical charts, and the association between protein expression, clinicopathological features and survival was investigated. Amongst 141 ovarian carcinoma samples, the loss of BECN1, LC3, and HMGB-1 expression was identified in 59 (41.8%), 35 (24.8%), and 66 (46.8%) samples, respectively. Clinicopathological factors were not significantly associated with the loss of BECN1 expression. However, significant associations were demonstrated between the expression of BECN1, LC3, and HMGB-1. In addition, loss of BECN1 expression demonstrated a significant association with poor progression-free and poor overall survival. Multivariate analysis demonstrated that loss of BECN1 expression and postoperative residual tumor were significant independent predictors of poor progression-free survival and poor overall survival. These results indicated that loss of BECN1 expression in ovarian carcinoma is a negative prognosticator in patients receiving platinum-based chemotherapy. Assessment of BECN1 expression may be useful for predicting an unfavorable response to platinum-based chemotherapy in ovarian carcinoma.

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