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Expression analysis of Wnt pathway associated genes in gastric cancer as a prognostic factor

Other Titles
 위암에서 예후인자로서 Wnt 신호전달계 연관유전자의 발현분석 
Authors
 김경민 
College
 College of Medicine (의과대학) 
Department
 Department of Medicine 
Degree
석사
Issue Date
2020
Abstract
서론 위암은 조직학적, 생물학적 특성이 매우 다양한 질병으로 최근 분자연구상 크게 4가지 그룹으로 분류되었고, 더 나아가 Wnt/β-catenin 신호전달계와 연관되어 있다는 것이 알려져 있다. 그러나 현재 위암에서 Wnt 연관 단백질의 발현과 예후의 관계에 관한 연구는 부족한 실정이다. 재료 및 방법 진행성위암 1158 케이스의 면역조직화학염색을 tissue microarray 에서 시행하였다. 사용한 항체는 CDX-1, CDX-2, XPNPEP3, TRIM24, Glutamine synthetase (GS), BMP-4, AXIN2, TCF4 이다.. 결과 전체 환자 중 69 (5.9%) 명은 EBV 양성, 113 (9.7%) 명은 현미부수체불안정성,,나머지 978 (84.3%) 명이 EBV음성 현미부수체 안정성 위암이었다. EBV양성 현미부수체불안정성 위암에서 CDX-1, CDX-2의 발현은 환자의 예후와 관계 없었다. 978명의 나머지 환자군에서 537 (54.9%) 명과 418 (42.7%) 명의 환자에서 CDX-2 와 CDX-1 이 발현되었다. 생존분석에서, CDX-1 와 CDX-2 발현은 환자의 좋은 예후와 유의하게 연관이 있었다. (다변량분석 p value=0.018 와 0.028). 그러나 다른 Wnt 연관 단백질, XPNPEP, TRIM24, GS, BMP-4, AXIN2, TCF4 에서는 통계적으로 유의하지 않았다. CDX-2 와 CDX-1 발현된 경우 Lauren 분류상 장형+혼합형, 미만형의 EBV음성 현미부수체안정성 위암에서 모두 좋은 생존율을 보였다 (log rank p; 0.010, 0.042 와 0.017, 0.017). 결론 CDX-1 및 CDX-2 의 발현은 EBV음성 현미부수체안정성 진행성 위암에서 좋은 예후인자이다 Introduction Gastric cancer (GC) is heterogeneous disease in terms of its histological findings and biological processes. It has recently been divided into four molecular subgroups, also involved in Wnt/β-catenin signaling pathway. However, the relationship between other Wnt-related proteins and the prognosis of gastric cancer has yet to be fully elucidated. Methods A large sample size (1158 cases of advanced GC (AGC)) was investigated using immunohistochemical staining and tissue microarray for the expression of CDX-1, CDX-2, XPNPEP3, TRIM24, glutamine synthetase (GS), BMP-4, AXIN2, and TCF4. Results Of the total cases, 69 (5.9%) were found to be EBV-positive, 113 (9.7%) were mismatch repair deficient (MMR-d), and the remaining 978 (84.3%) were EBV-negative MMR proficient (MMR-p) AGCs. In the EBV-positive and MMR-d groups, the expression of CDX-1 and CDX-2 had no relationship with patient outcome. Among the 978 EBV- MSS AGCs, 537 (54.9%) and 418 (42.7%) GCs were positive for CDX-2 and CDX-1 expression. Survival analysis demonstrated that CDX-1 and CDX-2 expression was correlated with a favorable patient outcomes in terms of overall survival (multivariate analysis; p-value = 0.018 and 0.028). However, other Wnt-related proteins, including XPNPEP3, TRIM24, GS, BMP-4, AXIN2, and TCF4, were not. The expression of CDX-2 and CDX-1 was associated with a favorable outcome in EBV-MSS intestinal/mixed and diffuse type GCs, respectively (log-rank p-value: 0.010, 0.042 and 0.017, 0.017). Conclusions The expression of CDX-1 and CDX-2 are favorable prognostic factors in EBV-negative MMR-p AGC.
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Appears in Collections:
1. College of Medicine (의과대학) > Others (기타) > 2. Thesis
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/181160
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