Multiomics profiling of buffy coat and plasma unveils diagnostic and predictive biomarkers for hepatocellular carcinoma
혈액 버피코트와 혈장 샘플의 다중 오믹스 분석을 통한 간세포암의 진단 및 치료 반응 예측 바이오마커 발굴
- 주제(키워드) hepatocellular carcinoma , buffy coat , plasma , multiomics , biomarker
- 주제(DDC) 570
- 발행기관 아주대학교 일반대학원
- 지도교수 임수빈
- 발행년도 2026
- 학위수여년월 2026. 2
- 학위명 박사
- 학과 및 전공 일반대학원 의생명과학과
- 실제URI http://www.dcollection.net/handler/ajou/000000035465
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
목차
I. INTRODUCTION 1
II. MATERIALS AND METHODS 6
A. Patient enrollment 6
B. Blood sample preparation 6
C. Whole transcriptome sequencing of buffy coat samples 7
D. Differential expression (DE) analyses of WTS data 8
E. Targeted proteome screening of plasma samples 8
F. Targeted methylome sequencing of buffy coat samples 9
G. Differential methylation (DM) analysis of targeted methylome sequencing data 10
H. Construction of a diagnostic signature 11
I. Construction of a predictive signature 11
J. DE analyses of publicly available bulk RNA-seq datasets 12
K. Rank-rank hypergeometric overlap (RRHO) 12
L. Single-cell RNA-seq analysis of GSE179795 and GSE195648 13
M. Single-cell RNA-seq analysis of GSE235863 13
N. Quantitative reverse transcription PCR (qRT‒PCR) 14
O. Area under the curve (AUC) analysis 15
III. RESULTS 16
Part 1. Etiology-specific diagnostic biomarkers for HCC 16
A. Study design 16
B. DE analyses of buffy coat WTS data 20
C. Construction and validation of a diagnostic gene signature 23
D. Validation of individual DEGs 28
E. DE analysis of targeted plasma proteome data 33
F. Single-cell analysis of the identified DEGs 37
Part 2. Predictive biomarkers for HCC immunotherapy 41
A. Study design 41
B. DE analysis of targeted plasma proteome data 44
C. Construction of a predictive gene signature 46
D. DM analysis of buffy coat methylome data 49
E. DE analyses of blood transcriptome datasets 52
IV. DISCUSSION 57
V. CONCLUSION 65
VI. REFERENCES 66
국문요약 75
