2019 Fiscal Year Final Research Report

Searching for molecular markers of postoperative recurrence after surgery for lung cancer and its clinical application

Research Project

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Project/Area Number	17K10803
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Respiratory surgery
Research Institution	Kanazawa Medical University
Principal Investigator	URAMOTO Hidetaka 金沢医科大学, 医学部, 教授 (90389445)
Co-Investigator(Kenkyū-buntansha)	薄田勝男金沢医科大学, 医学部, 教授 (00324046) 本野望金沢医科大学, 医学部, 講師 (30634901) 上田善道金沢医科大学, 医学部, 教授 (50271375) 町田雄一郎金沢医科大学, 金沢医科大学氷見市民病院, 助教 (50460366)
Project Period (FY)	2017-04-01 – 2020-03-31
Keywords	肺癌 / 術後再発 / TSHZ2 / PRDX4 / biomarker
Outline of Final Research Achievements	Surgery has reduced relapse, new tumors and deaths in patients with lung adenocarcinoma, but survival rate was still lower due to it’s characteristics of early metastasis and recurrence. we performed a microarray expression analysis using a combination of tumor tissues and cell lines based on recurrence or no-recurrence cases.We demonstrated the tumor-suppressive function of TSHZ2 in lung adenocarcinoma. TSHZ2 was found to be highly expressed in most lung adenocarcinoma cell lines and tumor tissues of lung adenocarcinoma patients. The overexpressed plasmids of TSHZ2 led to the dramatic inhibition of cell proliferation, colony formation ability, migration and apoptosis induction in lung adenocarcinoma cells. Notably, the high TSHZ2 expression patients with lung adenocarcinoma was inclined to have less EGFR mutations，but had preferable prognosis. Increased TSHZ2 could restrain EGFR and p-Erk1/2 expression, simultaneously activate p-SAPK/Jnk and p-P38 expression in vitro.
Free Research Field	呼吸器外科
Academic Significance and Societal Importance of the Research Achievements	完全切除はすなわち、完治、つまり再発がない根治ということを意味する。しかし、実際には種々の固形腫瘍で一定の割合で再発する。しかも肺癌の術後再発率は決して低くはない。しかし、病理組織学的評価、腫瘍マーカーなどの臨床的パラメーターはそれなりの再発の予測になるが、それらをもってしても全貌を説明可能ではない。また現在、肺癌では再発率を少しでも減らすために、術後補助化学療法が施行されているが、その真の恩恵を得るのは約5%にすぎない。つまり、再発するであろう、かつ、その薬剤の効果を期待できる母集団に限定される。本研究はその再発するであろう集団の特定につながると思われる。