Multiomics profiling of buffy coat and plasma unveils etiology-specific signatures in hepatocellular carcinoma

Hong, Jiwon; Eun, Jung Woo; Baek, Geum Ok; Cheong, Jae Youn; Park, Seryoung; Kim, Soon Sun; Cho, Hyo Jung; Lim, Su Bin

doi:.0..

Clin Mol Hepatol > Accepted Articles

Original Article

Multiomics profiling of buffy coat and plasma unveils etiology-specific signatures in hepatocellular carcinoma

Jiwon Hong^1,2, Jung Woo Eun³, Geum Ok Baek³, Jae Youn Cheong³, Seryoung Park¹, Soon Sun Kim³, Hyo Jung Cho³

, Su Bin Lim^1,2

¹Department of Biochemistry & Molecular Biology, Ajou University School of Medicine, Suwon 16499, Korea
²Department of Biomedical Sciences, Graduate School of Ajou University, Suwon 16499, Korea
³Department of Gastroenterology, Ajou University School of Medicine, Suwon 16499, South Korea

Correspondence :

Hyo Jung Cho ,
Tel: +82-31-219-7824, Fax: +82-31-219-5999, Email: pilgrim8107@hanmail.net
Su Bin Lim ,
Tel: +82-31-219-5056, Fax: +82-31-219-5059, Email: sblim@ajou.ac.kr

Received: January 17, 2024 Revised: March 12, 2024 Accepted: March 14, 2024
*Jiwon Hong and Jung Woo Eun contributed equally to this work.

ABSTRACT

Background/Aims
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Despite identification of several biomarkers for HCC diagnosis, challenges such as low sensitivity and intratumoral heterogeneity have impeded early detection, highlighting the need for etiology-specific blood biomarkers.
Methods
We generated whole-transcriptome sequencing (WTS) and targeted proteome data from buffy coat and plasma samples from HCC patients. By integrating etiological information on viral infection, we investigated the etiology-specific gene expression landscape at the blood level. Validation of differentially expressed genes (DEGs) was performed using publicly available RNA-seq datasets and qRT‒PCR with AUC analyses.
Results
Differential expression analyses with multiomics data revealed distinct gene expression profiles between HBV-associated HCC and nonviral HCC, indicating the presence of etiology-specific blood biomarkers. The identified DEGs were validated across multiple independent datasets, underscoring their utility as biomarkers. Additionally, single-cell RNA-seq analysis of HCC confirmed differences in DEG expression across distinct immune cell types.
Conclusions
Our buffy coat WTS data and plasma proteome data may serve as reliable sources for identifying etiology-specific blood biomarkers of HCC and might contribute to discovery of therapeutic targets for HCC across different etiologies.

KeyWords: hepatocellular carcinoma, buffy coat, plasma, transcriptomics, proteomics