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

2013 Fiscal Year Final Research Report

• 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
• Keywords: 癌 / ゲノム / 癌抑制遺伝子

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)
  • 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
• [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
• [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
• [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
• [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: Int J Gynecol Cancer Volume: 23 Pages: 60-64
• [Journal Article] Clinicopathological analysis of loss of AT-rich interactive domain 1A expression in endometrial cancer (2013)
  • 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 Pages: 103-109
• [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)
  • Author(s): Rahman MT, Nakayama K, Ishikawa M, Rahman M, Katagiri H, Katagiri A, Ishibashi T, Iida K, Yamada T, Miyazaki K
  • 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)
  • 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: 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)
  • Author(s): Katagiri A, Nakayama K, Rahman MT, Rahman M, Katagiri H, Ishikawa M, Ishibashi T, Iida K, Otsuki Y, Nakayama S, Miyazaki K
  • 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)
  • Author(s): Rahman MT, Nakayama K, Rahman M, Nakayama N, Ishikawa M, Katagiri A, Iida K, Nakayama S, Otsuki Y, Shih IeM, Miyazaki K
  • 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] 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
  • Journal Title: Tumour Biol. Volume: 32 Pages: 661-670
• [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
• [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