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

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

doi:10.3892/ol.2017.7379

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

Authors:
- 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
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Affiliations: Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Shimane 6938501, Japan, Department of Obstetrics and Gynecology, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka 4308558, Japan, Department of Pathology, Seirei Hamamatsu General Hospital, Hamamatsu, Shizuoka 4308558, Japan, Department of Organ Pathology, Shimane University School of Medicine, Izumo, Shimane 6938501, Japan
Published online on: November 9, 2017 https://doi.org/10.3892/ol.2017.7379
Pages: 1170-1176

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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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1	Allemani C, Weir HK, Carreira H, Harewood R, Spika D, Wang XS, Bannon F, Ahn JV, Johnson CJ, Bonaventure A, et al: Global surveillance cancer survival 1995–2009: Analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet. 385:977–1010. 2015. View Article : Google Scholar : PubMed/NCBI
2	American Cancer Sosiety, . Cancer Facts and Figures 2017. Atlanta, Ga: American Cancer Society; 2017
3	Pfisterer J and Ledermann JA: Management of platinum-sensitive recurrent ovarian cancer. Semin Oncol. 33 2 Suppl 6:S12–S16. 2006. View Article : Google Scholar : PubMed/NCBI
4	Nakayama K, Nakayama N and Miyazaki K: Development of a novel ovarian cancer molecular target therapy against cancer related transcriptional factor, NAC1. J Obstet Gynaecol Res. 39:18–25. 2013. View Article : Google Scholar : PubMed/NCBI
5	Agarwal R, Linch M and Kaye SB: Novel therapeutic agents in ovarian cancer. Eur J Surg Oncol (EJSO). 32:875–886. 2006. View Article : Google Scholar
6	Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000. View Article : Google Scholar : PubMed/NCBI
7	Shimizu S, Kanaseki T, Mizushima N, Mizuta T, Arakawa-Kobayashi S, Thompson CB and Tsujimoto Y: Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol. 6:1221–1228. 2004. View Article : Google Scholar : PubMed/NCBI
8	Rashmi R, Pillai SG, Vijayalingam S, Ryerse J and Chinnadurai G: BH3-only protein BIK induces caspase-independent cell death with autophagic features in Bcl-2 null cells. Oncogene. 27:1366–1375. 2008. View Article : Google Scholar : PubMed/NCBI
9	Furuya D, Tsuji N, Yagihashi A and Watanabe N: Beclin 1 augmented cis-diamminedichloroplatinum induced apoptosis via enhancing caspase-9 activity. Exp Cell Res. 307:26–40. 2005. View Article : Google Scholar : PubMed/NCBI
10	Sun Y, Liu JH, Jin L, Pan L, Sui YX, Yang Y and Shi H: Beclin 1 influences cisplatin-induced apoptosis in cervical cancer CaSki cells by mitochondrial dependent pathway. Int J Gynecol Cancer. 22:1118–1124. 2012. View Article : Google Scholar : PubMed/NCBI
11	Wang J: Beclin 1 bridges autophagy, apoptosis and differentiation. Autophagy. 4:947–948. 2008. View Article : Google Scholar : PubMed/NCBI
12	Eskelinen EL and Saftig P: Autophagy: A lysosomal degradation pathway with a central role in health and disease. Biochim Biophys Acta. 1793:664–673. 2009. View Article : Google Scholar : PubMed/NCBI
13	Mizushima N: Methods for monitoring autophagy. Int J Biochem Cell Biol. 36:2491–2502. 2004. View Article : Google Scholar : PubMed/NCBI
14	Tang D, Kang R, Cheh CW, Livesey KM, Liang X, Schapiro NE, Benschop R, Sparvero LJ, Amoscato AA, Tracey KJ, et al: HMGB1 release and redox regulates autophagy and apoptosis in cancer cells. Oncogene. 29:5299–5310. 2010. View Article : Google Scholar : PubMed/NCBI
15	Cai M, Hu Z, Liu J, Gao J, Liu C, Liu D, Tan M, Zhang D and Lin B: Beclin 1 expressin in ovarian tissues and its effect on ovarian cancer prognosis. Int Mol Sci. 15:5292–5303. 2014. View Article : Google Scholar
16	Odicino F, Pecorelli S, Zigliaani L and Creasman WT: History of the FIGO cancer staging system. Int J Gyneacol Obstet. 101:205–210. 2008. View Article : Google Scholar
17	Katagiri H, Nakayama K, Razia S, Nakamura K, Sato E, Ishibashi T, Ishikawa M, Iida K, Ishikawa N, Otsuki Y, et al: Loss of autophagy-related protein Beclin 1 may define poor prognosis in ovarian clear cell carcinomas. Int J Oncol. 47:2037–2044. 2015. View Article : Google Scholar : PubMed/NCBI
18	Katagiri A, Nakayama K, Rahman MT, Rahman M, Katagiri H, Nakayama N, Ishikawa M, Ishibashi T, Iida K, Kobayashi H, et al: Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma. Mod Pathol. 25:1–288. 2012.PubMed/NCBI
19	Nakayama K, Rahman MT, Rahman M, Yeasmin S, Ishikawa M, Katagiri A, Iida K, Nakayama N and Miyazaki K: Biological role and prognostic significance of NAC1 in ovarian cancer. Gynecol Oncol. 119:469–478. 2010. View Article : Google Scholar : PubMed/NCBI
20	Díaz-Montes TP and Bristow RE: Secondary cytoreduction for patients with recurrent ovarian cancer. Curr Oncol Rep. 7:451–458. 2005. View Article : Google Scholar : PubMed/NCBI
21	Harter P and du Bois A: The role of surgery in ovarian cancer with special emphasis on cytoreductive surgery for recurrence. Curr Opin Oncol. 17:505–514. 2005. View Article : Google Scholar : PubMed/NCBI
22	Gadducci A, Iacconi P, Cosio S, Fanucchi A, Cristofani R and Riccardo Genazzani A: Complete salvage surgical cytoreduction improves further survival of patients with late recurrent ovarian cancer. Gynecol Oncol. 79:344–349. 2000. View Article : Google Scholar : PubMed/NCBI
23	Gadducci A, Iacconi P, Fanucchi A, Cosio S, Teti G and Genazzani AR: Surgical cytoreduction during second-look laparotomy in patients with advanced ovarian cancer. Anticancer Res. 20:1959–1964. 2000.PubMed/NCBI
24	Zang RY, Li ZT, Tang J, Cheng X, Cai SM, Zhang ZY and Teng NN: Secondary cytoreductive surgery for patients with relapsed epithelial ovarian carcinoma: Who benefits? Cancer. 100:1152–1161. 2004. View Article : Google Scholar : PubMed/NCBI
25	Lin HX, Qiu HJ, Zeng F, Rao HL, Yang GF, Kung HF, Zhu XF, Zeng YX, Cai MY and Xie D: Decreased expression of Beclin 1 correlates closely with Bcl-xL expression and poor prognosis of ovarian carcinoma. PLoS One. 8:e605162013. View Article : Google Scholar : PubMed/NCBI
26	Zhou WH, Tang F, Xu J, Wu X, Yang SB, Feng ZY, Ding YG, Wan XB, Guan Z, Li HG, et al: Low expression of Beclin 1, associated with high Bcl-xL, predicts a malignant phenotype and poor prognosis of gastric cancer. Autophagy. 8:389–400. 2012. View Article : Google Scholar : PubMed/NCBI
27	Qiu DM, Wang GL, Chen L, Xu YY, He S, Cao XL, Qin J, Zhou JM, Zhang YX and E Q: The expression of beclin-1, an autophagic gene, in hepatocellular carcinoma associated with clinical pathological and prognostic significance. BMC Cancer. 14:3272014. View Article : Google Scholar : PubMed/NCBI
28	Giatromanolaki A, Koukourakis MI, Koutsopoulos A, Chloropoulou P, Liberis V and Sivridis E: High Beclin 1 expression defines a poor prognosis in endometrial adenocarcinomas. Gynecol Oncol. 123:147–151. 2011. View Article : Google Scholar : PubMed/NCBI
29	Nishikawa M, Miyake H, Liu B and Fujisawa M: Expression pattern of autophagy-related markers in non-metastatic clear cell renal cell carcinoma: Association with disease recurrence following radical nephrectomy. J Cancer Res Clin Oncol. 141:1585–1591. 2015. View Article : Google Scholar : PubMed/NCBI
30	Han Y, Xue XF, Shen HG, Guo XB, Wang X, Yuan B, Guo XP, Kuang YT, Zhi QM and Zhao H: Prognostic significance of Beclin-1 expression in colorectal cancer: A meta-analysis. Asian Pac J Cancer Prev. 15:4583–4587. 2014. View Article : Google Scholar : PubMed/NCBI
31	Rohatgi RA, Janusis J, Leonard D, Bellvé KD, Fogarty KE, Baehrecke EH, Corvera S and Shaw LM: Beclin 1 regulates growth factor receptor signaling in breast cancer. Oncogene. 34:5352–5362. 2015. View Article : Google Scholar : PubMed/NCBI