Role of KLF4 expression in gastric cancer.

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10492
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: University of Toyama
• Principal Investigator: Hashimoto Isaya 富山大学, 附属病院, 助教 (50649283)
• Co-Investigator(Kenkyū-buntansha): 奥村 知之 富山大学, 附属病院, 講師 (10533523) ; 長田 拓哉 富山大学, 附属病院, 講師 (40303242)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 胃癌の予後、治療予測 / サロゲートマーカー / 血中浮遊癌細胞 / KLF4 / iPS誘導因子

Outline of Final Research Achievements

To predict treatment effect and prognosis in gastric cancer, we analyzed the gastric cancer tissue and cells focusing at KLF4 and circulating tumor cells (CTC). In this study, the expression of KLF in human gastric cancer specimens were investigated by immunohistochemistry and analyzed with respect to clinicopathological characteristics, revealing that decreased KLF4 expression was associated with poor prognosis in these patients. In gastric cancer cell line, down regulation of KLF4(using SiRNA) showed enhancements of metastatic properties such as, cell migration and invasion.And we successfully identified CTCs in the gastric cancer patient. In this patient, resected specimen showed higher KLF4 expression but in the CTC analysis showed lower expression of KLF4 and E-Cadherin. KLF4 may exert a suppressive effect on the proliferation and metastasis of this type of cancer. Furthermore, the expression and activity of KLF4 in CSCs may be an important direction for cancer research .

Free Research Field

消化管外科学

Academic Significance and Societal Importance of the Research Achievements

胃癌切除組織を用いた解析で, iPS誘導因子のKLF4の胃癌組織での発現低下は,
強力な予後不良因子であった. また, 特殊なチップを用いて, 血中浮遊癌細胞の同定に成功した. 組織ではKLF4発現が低下しているが, 血中の癌細胞ではKLF4および転移能の１つの指標であるE-cadherinの発現の低下を認めた. 以上から胃癌がより予後不良となる転移能を獲得する状態ではKLF4の発現が関わっていることが示唆された. 今後は更にに研究を進め, 胃癌組織および血中浮遊癌細胞での, KLF4発現状況に応じた, 抗がん剤, 分子標的治療薬の効果予測が可能となれば, 新たな胃癌治療のツールとなり得る.