Loss of ARID1A, a tumor suppressor gene, expression is related to the mechanism of chemoresistance in ovarian clear cell carcinoma

• Project/Area Number: 23791844
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Shimane University
• Principal Investigator: ISHIKAWA MASAKO 島根大学, 医学部, 助教 (50467718)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 癌 / ゲノム / 癌抑制遺伝子 / 国際情報交流

Research Abstract

Recently, the ARID1A gene has been identified as a novel tumor suppressor in ovarian clear cell carcinoma (OCCC). The current study was designed to evaluate whether ARID1A was a prognostic factor for progression, survival, and chemoresistance in OCCC. Loss of ARID1A expression was identified in 9 (15.0%) of 60 OCCC samples. Loss of ARID1A correlated with shorter progression-free survival (PFS) (P<0.01) and tended to correlate with shorter overall survival in patients with OCCC treated with platinum-based chemotherapy. When data were stratified for the multivariate analysis, only the loss of ARID1A expression remained a significant predictor of reduced PFS (P=0.03). Tumors with loss of ARID1A were more likely to be chemoresistant than tumors with positive ARID1A (100.0 vs 40.0%, P=0.04). This study demonstrates that loss of ARID1A in OCCC is a negative prognostic factor in patients. Measurement of ARID1A expression may be a method to predict resistance in patients with OCCC.

Research Products

• [Journal Article] ESR1 gene amplification in endometrial carcinomas : A clinicopathological analysis (2013)
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• [Journal Article] KRAS and MAPK1 gene amplification in type II ovarian carcinomas (2013)
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• [Journal Article] Fatty acid synthase is a potential therapeutic target in estrogen receptor-/progesterone receptor-positive endometrioid endometrial cancer (2013)
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  • Journal Title: Oncology Volume: 84 Pages: 166-173
• [Journal Article] PPP2R1A mutation is a rare event in ovarian carcinoma across histological subtypes (2013)
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  • Journal Title: Anticancer Res. Volume: 33 Pages: 113-118
• [Journal Article] Is ATP7B a predictive marker in patients with ovarian carcinoma treated with platinum-taxane combination chemotherapy? (2013)
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• [Journal Article] Clinicopathological analysis of loss of AT-rich interactive domain 1A expression in endometrial cancer (2013)
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• [Journal Article] PPP2R1A mutation is a rare event in ovarian carcinoma across histological subtypes. (2013)
  • Author(s): Rahman M, Nakayama K, Rahman MT, Nakayama N, Katagiri H, Katagiri A, Ishibashi T, Ishikawa M, Iida K, Otsuki Y, Nakayama S, Miyazaki K.
  • Journal Title: Anticancer Res. Volume: 33 Pages: 113-118
  • Peer Reviewed
• [Journal Article] Is ATP7B a predictive marker in patients with ovarian carcinoma treated with platinum-taxane combination chemotherapy? (2013)
  • Author(s): Katagiri H, Nakayama K, Rahman MT, Rahman M, Katagiri A, Ishibashi T, Ishikawa M, Iida K, Nakayama S, Otsuki Y, Miyazaki K.
  • Journal Title: Cancer Res. Volume: 23 Pages: 60-64
  • Peer Reviewed
• [Journal Article] Fatty acid synthase is a potential therapeutic target in estrogen receptor-/progesterone receptor-positive endometrioid endometrial cancer. (2013)
  • Author(s): Rahman MT, Nakayama K, Ishikawa M, Rahman M, Katagiri H, Katagiri A, Ishibashi T, Iida K, Miyazaki K.
  • Journal Title: Oncology Volume: 84 Pages: 166-173
  • Peer Reviewed
• [Journal Article] KRAS and MAPK1 gene amplification in type II ovarian carcinomas. (2013)
  • Author(s): Rahman MT, Nakayama K, Rahman M, Katagiri H, Katagiri A, Ishibashi T, Ishikawa M, Sato E, Iida K, Nakayama N, Ishikawa N, Miyazaki K.
  • Journal Title: Int J Mol Sci. Volume: 14 Pages: 13748-13762
  • Peer Reviewed
• [Journal Article] ESR1 gene amplification in endometrial carcinomas: A clinicopathological analysis. (2013)
  • Author(s): Rahman MT, Nakayama K, Rahman M, Ishikawa M, Katagiri H, Katagiri A, Ishibashi T, Sato E, Iida K, Nakayama N, Ishikawa N, Miyazaki K.
  • Journal Title: Anticancer Res. Volume: 33 Pages: 3775-3781
  • Peer Reviewed
• [Journal Article] Notch3 overexpression as potential therapeutic target in advanced stage chemoresistant ovarian cancer (2012)
  • Author(s): Rahman MT, Nakayama K, Rahman M, Katagiri H, Katagiri A, Ishibashi T, Ishikawa M, Iida K, Nakayama S, Otsuki S, Miyazaki K
  • Journal Title: Am J Clin Pathol. Volume: 138 Pages: 535-544
• [Journal Article] NAC1, a BTB/POZ protein overexpressed in uterine sarcomas (2012)
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  • Journal Title: Anticancer Res. Volume: 32 Pages: 3841-3845
• [Journal Article] Gene amplification of ZNF217 located at chr20q13.2 is associated with lymph node metastasis in ovarian clear cell carcinoma (2012)
  • Author(s): Rahman MT, Nakayama K, Rahman M, Katagiri H, Katagiri A, Ishibashi T, Ishikawa M, Iida K, Nakayama N, Otsuki Y, Nakayama S, Miyazaki K
  • Journal Title: Anticancer Res. Volume: 32 Pages: 3091-3095
• [Journal Article] Clinicopathologic and biological analysis of PIK3CA mutation in ovarian clear cell carcinoma (2012)
  • Author(s): R ahman M, Nakayama K, Rahman MT, Nakayama N, Ishikawa M, Katagiri A, Iida K, Nakayama S, Otsuki Y, Shih IeM, Miyazaki K
  • Journal Title: Hum Pathol Volume: 43 Pages: 2197-2206
• [Journal Article] Fatty acid synthase expression associated with NAC1 is a potential therapeutic target in ovarian clear cell carcinomas (2012)
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  • Journal Title: Br J Cancer Volume: 107 Pages: 300-307
• [Journal Article] Frequent loss of tumor suppressor ARID1A protein expression in adenocarcinomas/adenosquamous carcinomas of the uterine cervix (2012)
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  • Journal Title: Int J Gynecol Cancer Volume: 22 Pages: 208-212
• [Journal Article] Prognostic and therapeutic impact of the chromosome 20q13.2 ZNF217 locus amplification in ovarian clear cell carcinoma (2012)
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  • Journal Title: Cancer Volume: 118 Pages: 2846-2857
• [Journal Article] Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma (2012)
  • Author(s): Katagiri A, Nakayama K, Rahman MT, Rahman M, Katagiri H, Nakayama N Ishikawa M, Ishibashi T, Iida K, Otsuki Y, Nakayama S, Miyazaki K
  • Journal Title: Mod Pathol. Volume: 25 Pages: 282-288
• [Journal Article] Biological and clinical significance of NAC1 expression in cervical carcinomas : a comparative study between squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas (2012)
  • Author(s): Yeasmin S, Nakayama K, Rahman MT, Rahman M, Ishikawa M, Katagiri A, Iida K, Nakayama N, Otsuki Y, Kobayashi H, Nakayama S, Miyazaki K
  • Journal Title: Hum Pathol. Volume: 43 Pages: 506-519
• [Journal Article] Frequent loss of tumor suppressor ARID1A protein expression in adenocarcinomas/adenosquamous (2012)
  • Author(s): Katagiri A, Nakayama K, Rahman MT, Rahman M, Katagiri H, Ishikawa M, Ishibashi T, Iida K, Otsuki Y, Nakayama
  • Journal Title: Int J Gynecol Cancer Volume: 22 Issue: 2 Pages: 208-212
  • DOI: 10.1097/igc.0b013e3182313d78
  • Peer Reviewed
• [Journal Article] Clinicopathologic analysis of loss of AT-rich interactive domain 1A expression in endometrial cancer (2012)
  • Author(s): Rahman M, Nakayama K, Rahman MT, Katagiri H, Katagiri A, Ishibashi T, Ishikawa M, Iida K, Miyazaki K
  • Journal Title: Hum Pathol. Volume: 44 Issue: 1 Pages: 103-109
  • DOI: 10.1016/j.humpath.2012.04.021
  • Peer Reviewed
• [Journal Article] Loss of ARID1A expression is related to patient shorter progression-free survival and chemoresistance (2012)
  • Author(s): Katagiri A, Nakayama K, Rahman MT, Rahman M, Katagiri H, Ishikawa M, Ishibashi T, Iida K, Otsuki Y, Nakayama
  • Journal Title: Mod Pathol. Volume: 25 Issue: 2 Pages: 282-288
  • DOI: 10.1038/modpathol.2011.161
  • Peer Reviewed
• [Journal Article] Prognostic and therapeutic impact of amplification of the chr20q13.2 ZNF217 locus in ovarian (2012)
  • Author(s): Rahman MT, Nakayama K, Rahman M, Nakayama N, Ishikawa M, Katagiri A, Iida K, Nakayama S, Otsuki Y,
  • Journal Title: Cancer Volume: 118 Issue: 11 Pages: 2846-2857
  • DOI: 10.1002/cncr.26598
  • Peer Reviewed
• [Journal Article] Gene amplification of ZNF217 located at chr20q13.2 is associated with lymph node metastasis in ovarian clear cell carcinoma. (2012)
  • Author(s): Rahman MT, Nakayama K, Rahman M, Katagiri H, Katagiri A, Ishibashi T, Ishikawa M, Iida K, Nakayama N, Otsuki Y, Nakayama S, Miyazaki K.
  • Journal Title: Anticancer Res. Volume: 32 Pages: 3091-3095
  • Peer Reviewed
• [Journal Article] A Case of Stage IVb Cervical Carcinoma in Which Survival Was Prolonged by Two Different Chemotherapies and CCRT. (2012)
  • Author(s): Ishikawa M, Nakayama K, Rahman MT, Rahman M, Katagiri A, Katagiri H, Ishibashi T, Iida K, Miyazaki K
  • Journal Title: Gan To Kagaku Ryoho Volume: 39 Pages: 451-455
  • Peer Reviewed
• [Journal Article] MKK4 acts as a potential tumor suppressor in ovarian cancer. (2012)
  • Author(s): Yeasmin S, Nakayama K, Rahman MT, Rahman M, Ishikawa M, Katagiri A, Iida K, Nakayama N, Miyazaki K
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• [Journal Article] Loss of ARID1A expression is related to syorter progression-free survival and chemoresistance in ovarian clear cell carcinoma. (2012)
  • Author(s): Katagiri A, Nakayama K, Rahman MT, Rahman M, Karagiri H, Nakayama N, Ishikawa M, Ishibashi T, Iida K, Kobayashi H, Otsuki Y, Nakayama S, Miyazaki K.
  • Journal Title: Mod Pathol. Volume: 25 Pages: 282-288
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• [Journal Article] Uterine leiomyosarcoma producing granulocyte colony stimulating factor. (2012)
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• [Journal Article] Biological and clinical significance of NAC1 expression in cervical carcinomas: a comparative study between squamous cell carcinomas and adenocarcinomas/adenosquamous carcinomas. (2012)
  • Author(s): Yeasmin S, Nakayama K, Rahman MT, Rahman M, Ishikawa M, Katagiri A, Iida K, Nakayama N, Otuski Y, Kobayashi H, Nakayama S, Miyazaki K
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• [Journal Article] EGFR gene amplification is related to adverse clinical outcomes in cervical squamous cell carcinoma, making the EGFR pathway a novel therapeutic target (2011)
  • Author(s): Iida K, Nakayama K, Rahman MT, Rahman M, Ishikawa M, Katagiri A, Yeasmin S, Otsuki Y, Kobayashi H, Nakayama S, Miyazaki K
  • Journal Title: Br J Cancer Volume: 105 Pages: 420-427
• [Journal Article] MKK4 acts as a potential tumor suppressor in ovarian cancer (2011)
  • Author(s): Yeasmin S, Nakayama K, Rahman MT, Rahman M, Ishikawa M, Katagiri A, Iida K, Nakayama N, Miyazaki K
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• [Journal Article] Loss of MKK4 expression in ovarian cancer : a potential role for the epithelial to mesenchymal transition (2011)
  • Author(s): Yeasmin S, Nakayama K, Rahman MT, Rahman M, Ishikawa M, Katagiri A, Iida K, Nakayama N, Miyazaki K
  • Journal Title: Int J Cancer Volume: 128 Pages: 94-104
• [Journal Article] A case of postoperative rapid brain metastasis originating from stage II a cervical adenosquamous cell carcinoma. (2011)
  • Author(s): Ishikawa M, Nakayama K, Rahman MT, Rahman M, Katagiri A, Iida K, Miyazaki K
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• [Journal Article] EGFR gene amplification is related to adverse clinical outcomes in cervical squamous cell carcinoma, making the EGFR pathway a novel therapeutic target. (2011)
  • Author(s): Iida K, Nakayama K, Rahman MT, Rahman M, Ishikawa M, Katagiri A, Yeasmin S, Otsuki Y, Kobayashi H, Nakayama S, Miyazaki K
  • Journal Title: Br J Cancer. Volume: 105 Pages: 420-427
  • Peer Reviewed
• [Journal Article] Loss of MKK4 expression in ovarian cancer: a potential role for the epithelial to mesenchymal transition. (2011)
  • Author(s): Yeasmin S, Nakayama K, Rahman MT, Rahman M, Ishikawa M, Katagiri A, Iida K, Nakayama N, Miyazaki K
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  • Peer Reviewed
• [Journal Article] A comparative study between microwave endometrial ablation and conventional surgical procedures for treatment of menorrhagia. (2011)
  • Author(s): Nakayama K, Yeasmin S, Katagiri A, Rahman MT, Rahman M, Ishikawa M, Iida K, Nakayama N, Aoki S, Miyazaki K
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  • NAID: 130001157662
  • Peer Reviewed
• [Presentation] 卵巣癌におけるNAC1 pathwayに基づいた創薬への展開、(婦人科がんにおけるトランスレーショナルリサーチ、シーズの探索から臨床応用まで) (2013)
  • Author(s): 石川雅子,中山健太郎、中山真美、片桐浩、片桐敦子、佐藤絵美、飯田幸司、Mohammed Tanjimur Rahman、Munmun Rahman、宮崎康二
  • Organizer: The 3rd Biennial Meeting of ASGO
  • Place of Presentation: ウエスティン都ホテル京都、京都市
  • Year and Date: 2013-12-15
• [Presentation] 卵巣癌におけるNAC1 pathwayに基づいた創薬への展開、(婦人科がんにおけるトランスレーショナルリサーチ、シーズの探索から臨床応用まで) (2013)
  • Author(s): 中山健太郎、中山真美、石川雅子、片桐浩、片桐敦子、佐藤絵美、飯田幸司、Mohammed Tanjimur Rahman、Munmun Rahman、宮崎康二
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜、横浜市
  • Year and Date: 2013-10-03
• [Presentation] 新規癌関連転写因子NAC1を標的とした卵巣癌治療法の開発、(卵巣癌のMolecular Medicine) (2013)
  • Author(s): 中山健太郎、石川雅子、片桐浩、片桐敦子、石橋朋佳、佐藤絵美、Mohammed Tanjimur Rahman、Munmun Rahman、飯田幸司、中山真美、宮崎康二
  • Organizer: 第54回日本婦人科腫瘍学会
  • Place of Presentation: ホテルグランパシフィックLE DAIBA、東京
  • Year and Date: 2013-07-20
• [Presentation] 婦人科悪性腫瘍に合併したTrousseau症候群の3例 (2013)
  • Author(s): 石川雅子,中山健太郎,佐藤絵美,片桐 浩,片桐敦子,飯田幸司,宮崎康二
  • Organizer: 第65回 日本産科婦人科学会学術講演会
  • Place of Presentation: 札幌
• [Presentation] 骨外性Ewing肉腫を疑う1例 (2013)
  • Author(s): 石川雅子,中山健太郎,佐藤絵美,片桐 浩,片桐敦子,飯田幸司,宮崎康二
  • Organizer: 第54回 日本婦人科腫瘍学会学術講演会
  • Place of Presentation: 東京
• [Presentation] Fatty Acid Synthase expression associated with NAC1 is a potential therapeutic target in Ovarian Clear Cell Carcinomas (2013)
  • Author(s): 石川雅子,中山健太郎,Mohammed Tanjimur Rahman, Munmun Rahman,佐藤絵美,片桐 浩,片桐敦子,飯田幸司,中山真美,宮崎康二
  • Organizer: 第12回 婦人科がん分子標的研究会学術集会
  • Place of Presentation: 奈良
• [Presentation] 婦人科悪性腫瘍に合併したTrousseau症候群の4例 (2013)
  • Author(s): 石川雅子,中山健太郎,佐藤絵美,片桐 浩,片桐敦子,飯田幸司,宮崎康二
  • Organizer: 第51回 癌治療学会学術講演会
  • Place of Presentation: 京都
• [Presentation] Fatty Acid Synthase expression associated with NAC1 is a potential therapeutic target in Ovarian Clear Cell Carcinomas (2013)
  • Author(s): 石川雅子,中山健太郎,Mohammed Tanjimur Rahman, Munmun Rahman,佐藤絵美,片桐 浩,片桐敦子,飯田幸司,中山真美,宮崎康二
  • Organizer: The 3rd ASGO (Asian Society of Gynecologic Oncology )
  • Place of Presentation: 京都
• [Presentation] 卵巣癌におけるMKK4発現消失はEMT(Epithelial to mesenchymal transition)を生じ腹膜播種に関与する (2011)
  • Author(s): 石川雅子、中山健太郎、Mohammed Tanjimur Rahman、Munmun Rahman、片桐敦子、片桐浩、飯田幸司、石橋朋佳、宮崎康二
  • Organizer: 第63回 日本産科婦人科学会学術講演会
  • Place of Presentation: 大阪国際会議場
• [Presentation] 卵巣癌におけるMKK4発現の低下はEMT(Epithelial to mesenchymal transition)を生じ腹膜播種に関与する (2011)
  • Author(s): 石川雅子、中山健太郎、Mohammed Tanjimur Rahman、Munmun Rahman、片桐敦子、片桐浩、飯田幸司、石橋朋佳、宮崎康二
  • Organizer: 第10回 日本婦人科がん分子標的研究会学術集会
  • Place of Presentation: 松江市ホテル一畑
• [Book] 産婦人科の実際 (2012)
  • Author(s): 石川雅子、中山健太郎、石橋朋佳、片桐浩、片桐敦子、宮崎康二
  • Total Pages: 8
  • Publisher: 金原出版株式会社