Chromosomal instability in colorectal cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08963
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Fukushima Medical University
• Principal Investigator: Fujita Shotaro 福島県立医科大学, 医学部, 博士研究員 (20769640)
• Co-Investigator(Kenkyū-buntansha): 岡山 洋和 福島県立医科大学, 医学部, 講師 (20583397) ; 芦澤 舞 福島県立医科大学, 医学部, 助教 (10791535)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 大腸癌 / 染色体不安定性

Outline of Final Research Achievements

Colorectal cancer (CRC) is often characterized by chromosomal instability (CIN). In the present study, we investigated a set of candidate genes that are associated with tumor progression and immune suppression in CIN CRC, using multi-omics analysis, immunohistochemistry and in vitro functional assays. Among several candidates , we found that PAICS was significantly downregulated during tumor progression in CIN CRCs, potentially due to loss of chromosome 4 or chromosome arm 4q. Furthermore, we also demonstrated that the downregulation of this gene at transcriptional and protein levels was associated with poor survival outcomes. However, the functional roles of this gene remain to be elucidated, and our future studies will address the other candidate genes that are associated with immune suppression particularly in CIN CRCs.

Free Research Field

大腸癌

Academic Significance and Societal Importance of the Research Achievements

多くの大腸癌は複数の遺伝子変異の蓄積と同時に染色体不安定性を示す。本研究では、染色体不安定性を示す大腸癌における特定の染色体の欠失とそれに関連する遺伝子発現低下、さらにその臨床的意義を示すことができた。大腸癌の発癌・進展における生物学的機構の解明や、大腸癌治療の個別化を目指す今後の癌研究の礎として寄与し得ると考える。