유전자발현 프로파일링을 통한 피부 기저세포암의 분자학적 분류
Molecular Classification of Basal Cell Carcinoma of Skin by Gene Expression Profiling
- 주제(키워드) non-melanoma skin cancer , basal cell carcinoma , squamous cell carcinoma , gene expression profiling , heterogeneity
- 발행기관 아주대학교
- 지도교수 박명철
- 발행년도 2015
- 학위수여년월 2015. 8
- 학위명 박사
- 학과 및 전공 일반대학원 의학과
- 실제URI http://www.dcollection.net/handler/ajou/000000020397
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Non-melanoma skin cancers (NMSC) including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are more common kinds of skin cancer. Although these tumors share common pathological and clinical features, their similarity and heterogeneity at molecular levels are not fully elaborated yet. Here, by performing comparative analysis of gene expression profiling of BCC, SCC, and normal skin tissues, we could classify the BCC into three subtypes of classical, SCC-like, and normal-like BCCs. Functional enrichment and pathway analyses revealed the molecular characteristics of each subtype. The classical BCC showed the enriched expression and transcription signature with the activation of Wnt and Hedgehog signaling pathways, which were well known key features of BCC. By contrast, the SCC-like BCC was enriched with immune-response genes and oxidative stress-related genes. Network analysis revealed the PLAU/PLAUR as a key regulator of SCC-like BCC. The normal-like BCC showed prominent activation of metabolic processes particularly the fatty acid metabolism. The existence of these molecular subtypes could be validated in an independent dataset, which demonstrated the three subgroups of BCC with distinct functional enrichment. In conclusion, we suggest a novel molecular classification of BCC providing insights on the heterogeneous progression of BCC.
more목차
ABSTRACT i
TABLE OF CONTENTS ii
LIST OF FIGURES iii
LIST OF TABLES iv
ABBREVIATION v
I. INTRODUCTION 1
II. MATERIALS AND METHODS 4
A. Clinical samples 4
B. Gene expression profiling 4
C. Analysis of microarray data 5
D. Immunohistochemistry 5
III. RESULTS 7
A. Comparison of gene expression profiles of SCC and BCC 7
B. The functional characteristics of molecular subtypes 10
C. External validation of the gene expression profiling analysis 18
D. PLAU is a putative key regulator of SCC-like BCC 28
IV. DISCUSSION 30
REFERENCES 32
국문요약 38
