Development of innovative diagnostic and therapeutic methods for esophageal squamous cell carcinoma focusing on genomic abnormalities

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17012
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Chiba University
• Principal Investigator: Akizue Naoki 千葉大学, 医学部附属病院, 医員 (40836110)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 食道扁平上皮癌 / 内視鏡治療後瘢痕 / 遺伝子変異

Outline of Final Research Achievements

The study cohort included 19 patients with ESCC. We used an EC panel to identify target sequences for squamous cell carcinoma (SCC), background mucosa (BM), and RM, respectively, after ER of ESCC.
Results: We identified 77 mutations of 32 genes in SCC, 133 mutations of 34 genes in BM, and 100 mutations of 29 genes in RM. Putative driver mutations were identified in 20 mutations in 14 cases in SCC, 16 mutations in 10 cases in BM, and 7 mutations in 11 cases in RM. The rate of putative driver mutations to total mutations was significantly lower in RM (26% in SCC vs. 12% in BM vs. 7% in RM, p = 0.009). Additionally, the rate of cases with TP53 putative driver mutations was significantly lower in RM (63% in SCC vs. 37% in BM vs. 16% in RM, p = 0.011). The percentage of putative driver mutations and percentage of cases with a putative driver of TP53 were significantly lower in RM.
Conclusion: Esophageal RM after ER of ESCC could have a lower risk of carcinogenesis.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

食道扁平上皮癌は非常に致死率の高い癌である。飲酒や喫煙がリスクファクターとなり、リスクが高い患者では同時に多発したり、異時性に再発することがしばしばある。早期の食道扁平上皮癌に対しては内視鏡的切除が近年多く施行されているが、予防法は確立されていない。一度慢性炎症を起こしてしまった食道は発癌リスクが高いため、何年にもわたり内視鏡検査での経過観察が必要なる。そこで内視鏡切除の瘢痕部の遺伝子変異を調べることで、一度欠損し、再生してきた粘膜面では発癌リスクがやや減少することが本研究では示唆された。