Molecular alterations and targeted therapy in pancreatic ductal adenocarcinoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22851
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: University of the Ryukyus
• Principal Investigator: Kawamata Futoshi 琉球大学, 医学(系)研究科(研究院), 助教 (70825629)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 膵癌 / 遺伝子解析 / ドライバー遺伝子 / hCGβ

Outline of Final Research Achievements

Pancreatic cancer is one of the most common causes of cancer-related deaths. The 4 main driver genes of pancreatic cancer are KRAS, TP53, CDKN2A, and SMAD4. We previously reported that amplification of the clinically actionable genes ERBB2 and FGFR1 was observed in the metastatic tissue of patients but not in the paired primary colorectal cancer. In the present study, we analyzed the correlation between hCGβ expression and clinicopathological features in pancreatic cancer. hCGβ expression was the only independent factor for overall survival (P = 0.0019). Moreover, hCGβ-downregulated cell lines had significantly reduced proliferative ability and invasion capacity. Moreover, the expression of cadherin was upregulated, and the expressions of the slug, and α-SMA were downregulated in the hCGβ shRNA-transfected pancreatic cancer cell lines. In summary, hCGβ promotes the EMT signaling pathway, which in turn stimulates pancreatic cancer invasion and metastasis.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

膵癌は極めて予後不良な悪性疾患である。特に、門脈系浸潤を伴う切除可能境界(borderline resectable:BR) 膵癌に対する治療に関しては外科的な解剖学的因子のみならず、ゲノム解析による膵癌の宿主側因子を取り入れることで、術前治療を含む最適な治療戦略を構築できる可能性がある。今回、我々の研究においては、膵癌におけるhCGβ発現が術後の予後や再発に関与する可能性が示唆されたため、術前遺伝子解析によりhCGβのコピー数の増加や遺伝子変異を認めた症例に関しては、術前化学放射線療法（CRT）を選択したり、術前化学療法の期間を長くすることで膵癌の長期予後を改善できる可能性がある。