Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Prognostication by Cluster Analysis of COX-2, MMP-9 and P53 Expression and by Clinico-pathologic Correlation Analysis in Non-small Cell Lung Cancer

비소세포폐암에서 COX-2,MMP-9와 돌연변이형 p53 의 발현이 생존에 대한 예후 분석

  • Shin, Jong Wook (Division of Allergy, Respiratory and Critical Care Medicine, Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Choi, Jae Ho (Department of Pathology, Chung-Ang University College of Medicine) ;
  • Park, In Won (Division of Allergy, Respiratory and Critical Care Medicine, Department of Internal Medicine, Chung-Ang University College of Medicine) ;
  • Yoo, Jae Hyung (Department of Pathology, Chung-Ang University College of Medicine)
  • 신종욱 (중앙대학교 의과대학 내과학교실) ;
  • 최재호 (중앙대학교 의과대학 병리학교실) ;
  • 박인원 (중앙대학교 의과대학 내과학교실) ;
  • 유재형 (중앙대학교 의과대학 병리학교실)
  • Received : 2007.05.03
  • Accepted : 2007.05.03
  • Published : 2007.07.30
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Abstract

Background: In pathogenesis and prognosis of lung cancer, significance of enormous types of genetic expression were very compounding and undetermined. We performed this study to search association between clinical characteristics and expression of COX-2, MMP-9 and p53 in non-small cell lung cancer. Methods: Ninety-one patients with adenocarcinoma or squamous cell carcinoma were enrolled. We had searched clinical data retrospectively and performed immunohistochemical staining for COX-2, MMP-9 and p53. We had analyzed significance of these three genes in clinical features and prognosis for survival. Results: 1) In squamous cell carcinoma, male was predominant and was significantly correlated with smoking. 2) Major prognostic determinants for overall survival were curative resection. 3) Expression of COX-2 was more frequent in adenocarcinoma than in squamous cell carcinoma. 4) Negative staining of COX-2, MMP-9 and p53 was more frequent in squamous cell carcinoma than adenocarcinoma. 5) Survival duration was longer in the group with positive expression of p53 and negative for COX-2 and MMP-9 (median duration of survival = 165.6 weeks) than groups with the other expressional patterns. 6) Significant correlation was found between expression of MMP-9 and COX-2. In squamous cell carcinoma, expression of MMP-9, COX-2 and mutant p53 were mutually correlated. 7) COX-2 expression was significant prognostic factor for survival in resected cancer group. In unresected inoperable non-small cell lung cancer group, MMP-9 was statistically significant prognostic factor for overall survival. Conclusion: COX-2 and MMP-9 might have some roles for progression or prognosis in some selected patients with non-small cell lung cancer. COX-2 and MMP-9 may have some roles for disease progression or prognosis in selected patients with NSCLC.

연구배경: 폐암의 병인에 기여하거나 예후를 결정하는 인자에 대해서는 매우 다양한 인자와 다양한 상호 관계로 인하여 특히 유전자의 역할에 대해서는 결정적으로 알려진 것이 없어 앞으로 더 많은 연구가 필요한 실정이다. 이에 따라 본 연구에서는 COX-2, MMP-9, p53가 비소세포폐암에서 어떻게 발현되는지 세포면역학적으로 알아보고 임상 특성과 예후와 상관관계를 알아보고자 하였다. 대상 및 방법: 91명의 비소세포폐암을 대상으로 하여 후향적으로 임상특성을 고찰하고 COX-2, MMP-9, p53의 유전자 표현을 세포면역학적 방법을 통하여 검사하였다. 임상특성과 유전자 표현 패턴의 상관관계와 생존에 대한 예후인자로서의 역할에 대하여 조사하였다. 결 과: 1) 편평상피세포암에서는 흡연자과 남자가 우세한 비율을 차지하였으며 남자에서 흡연의 비율이 유의하게 높았다. 2) 전체 대상 환자에서 생존에 영향을 미치는 결정적인 인자는 근치적 절제술의 시행여부와 병기로 나타났다. 3) COX-2의 발현은 편평상피세포암 보다 선암에서 더 유의하게 높게 발현되었다. 4) COX-2, MMP-9, p53의 발현이 모두 되지 않는 비율은 선암에 비해 편평상피세포암에서 더 흔하게 관찰되었다. 5) p53돌연변이가 있으면서 COX-2와 MMP-9은 발현이 되지 않는 비소세포폐암환자의 생존기간이 다른 발현 양상을 보이는 경우에서의 생존기간보다 더 연장되어 보였다(생존기간의 중앙값; 165.6주). 6) COX-2의 발현과 MMP-9의 발현 사이에는 유의한 상관관계가 있었다. 7) 폐암을 근치적으로 절제한 환자의 경우에 COX-2의 발현은 유의한 예후인자였다. MMP-9는 근치적 절제술을 받지 못한 환자군에서 유의한 예후인자로 작용하였다.

Keywords

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