Molecular Biological Differences in Left-Sided and Right-Sided Colorectal Cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15997
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: The University of Tokushima
• Principal Investigator: KAGEMOTO Kaizo 徳島大学, 病院, 特任助教 (60933356)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 大腸癌 / オルガノイド

Outline of Final Research Achievements

In this study, we aimed to elucidate the molecular biological differences between right-sided and left-sided colon cancer. Right-sided colon cancer organoids demonstrated significantly higher cell proliferation activity and invasive potential compared to left-sided organoids. Additionally, mRNA expression analysis revealed that TIMP1 was significantly upregulated in right-sided colon cancer organoids compared to the left side. Western blot analysis confirmed high expression of TIMP1 protein in all cases of right-sided colon cancer, whereas TIMP1 protein was barely detectable in left-sided colon cancer. TIMP1 has been reported to be involved in tumor formation through the FAK/Akt pathway and MAPK pathway, suggesting its potential role in proliferation, invasion, and prognosis of right-sided colon cancer.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

右側大腸癌は左側に比較し予後不良であり、左右大腸癌の分子生物学的差異の解明は大きな課題である。本研究では右側大腸癌オルガノイドの細胞増殖能, 浸潤能が高いこと、また、右側大腸癌オルガノイドではTIMP1が高発現していることを見出した。今後は、オルガノイドを用いてin vivo, invitroで活性化パスウェイに対する薬剤感受性を評価する事で、治療困難とされる右側大腸癌の薬剤選択や治療薬開発につながると考えられる。