Exploring the effect of chemoradiotherapy on caner microenvironment and its clinical application in patients with pancreatic adenocarcinoma

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K19881
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Mie University
• Principal Investigator: Murata Yasuhiro 三重大学, 医学部附属病院, 講師 (20572655)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 浸潤性膵管癌 / 化学放射線治療 / 組織学的効果 / 細胞外マトリックス / Tenascin-C / 癌微小環境

Outline of Final Research Achievements

Tenascin-C (TN-C) is an extracellular matrix protein that is up-regulated in pancreatic ductal adenocarcinoma (PDAC) stroma and associated with tumor invasion. We examined intratumor stromal expression of TN-C in resected specimens as a indicator of histological response to chemoradiotherapy (CRT) and prognosis in locally advanced unresectable (UR-LA) PDAC. TN-C expression was immunohistologically evaluated in 45 UR-LA PDAC patients who underwent resection after CRT and 12 who underwent up-front surgery. The intratumor expression of TN-C is significantly higher in the naive tumor tissue for 12 patients with up-front surgery than that for 45 UR-LA PDAC patients who were treated with CRT. Tenascin-C expression was inversely correlated with histologic response to CRT. In multivariate analysis, TN-C expression was a significant prognostic factor. Intratumor expression of TN-C may be useful as a surrogate for histological response and prognosis in PDAC patients with resection after CRT.

Free Research Field

膵臓外科学

Academic Significance and Societal Importance of the Research Achievements

膵癌は予後不良の難治性消化器癌であり、外科治療のみではなく化学療法や放射線治療を主軸とした集学的治療の重要性が注目されている。膵癌に対する術前治療の組織学的効果は、切除前に評価することが困難であり、治療成績の向上のためには組織学的効果を反映するマーカーの同定が必要である。本研究の結果、膵癌間質内TNC発現は術前治療の組織学的効果判定や予後予測に有用な surrogate markerである可能性が示唆された。今後、血清や超音波内視鏡下穿刺吸引細胞診などによる腫瘍内TNC発現のモニタリングが可能となれば、治療効果判定や切除適応決定など臨床応用が期待され、膵癌の予後改善に貢献することが期待される。