Identification of biomarkers by RNAi screening that predict efficacy of chemotherapy in esophageal cancer

• Project/Area Number: 26430146
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Arakawa Yasuhiro 東京慈恵会医科大学, 医学部, 講師 (80349547)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2016: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 食道癌 / 薬剤感受性 / 薬剤耐性 / RNAiスクリーニング / 癌化学療法 / 化学療法 / 効果予測 / シスプラチン / フッ化ピリミジン / タキサン

Outline of Final Research Achievements

In this study, we explored genes whose knockdown promotes esophageal cancer cells increased sensitivity or resistance to anticancer drugs using genome-wide RNA interference screening.
First, we performed positive-selection screening. We infected esophageal cancer cells (KYSE170) with shRNA pool and then treated cells with cisplatin. We obtained a dozen sublines from KYSE170 that were resistant to cisplatin. We identified genes whose inhibition rendered esophageal cells resistant to cisplatin.
Next, we performed negative-selection screening. We divided shRNA-infected KYSE170 cells into two groups and administered cisplatin to one group. Then we compared the abundance of each shRNA. We found that the inhibition of genes involved in nucleotide excision repair and histone modification increased cisplatin sensitivity of esophageal cancer cells.

Research Products

• [Journal Article] Early Response of Esophageal Cancer to Neoadjuvant Chemotherapy with Docetaxel-Cisplatin-5-Fluorouracil Represents Sensitivity: A Phase II Study. (2016)
  • Author(s): Matsumoto A, Nishikawa K, Yuda M, Tanaka Y, Tanishima Y, Arakawa Y, Ishibashi Y, Sakuyama T, Omura N, Mitsumori N, Aiba K, Yanaga K.
  • Journal Title: Anticancer Res. Volume: 36(4) Pages: 1937-42
  • Peer Reviewed
• [Journal Article] Antimyeloma activity of bromodomain inhibitors on the human myeloma cell line U266 by downregulation of MYCL. (2016)
  • Author(s): Suzuki K, Yamamoto K, Arakawa Y, Yamada H, Aiba K, Kitagawa M.
  • Journal Title: Anticancer Drugs. Volume: 27(8) Issue: 8 Pages: 756-65
  • DOI: 10.1097/cad.0000000000000389
  • Peer Reviewed