American Association for Cancer Research
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Supplementary Tables from Dynamics of Genomic, Epigenomic, and Transcriptomic Aberrations during Stepwise Hepatocarcinogenesis

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journal contribution
posted on 2023-03-31, 03:42 authored by Byul A Jee, Ji-Hye Choi, Hyungjin Rhee, Sarah Yoon, So Mee Kwon, Ji Hae Nahm, Jeong Eun Yoo, Youngsic Jeon, Gi Hong Choi, Hyun Goo Woo, Young Nyun Park

Supplementary Table S1: Tissue specimens used for RNA-seq analysis. Supplementary Table S2: Tissues specimens used for immunohistochemical analysis. Supplementary Table S3: Gene signatures used in the study. Supplementary Table S4: Differentially methylated probes during hepatocarcinogenesis. Supplementary Table S5: Univariate and multivariate analysis for SPINK1 expression and HCC clinico-pathological features in TCGA-LIHC data.


Research Foundation of Korea



Hepatocellular carcinoma (HCC) undergoes a stepwise progression from liver cirrhosis to low-grade dysplastic nodule (LGDN), high-grade dysplastic nodule (HGDN), early HCC (eHCC), and progressed HCC (pHCC). Here, we profiled multilayered genomic, epigenomic, and transcriptomic aberrations in the stepwise hepatocarcinogenesis. Initial DNA methylation was observed in eHCC (e.g., DKK3, SALL3, and SOX1) while more extensive methylation was observed in pHCC. In addition, eHCCs showed an initial loss of DNA copy numbers of tumor suppressor genes in the 4q and 13q regions, thereby conferring survival benefits to cancer cells. Transcriptome analysis revealed that HGDNs expressed endoplasmic reticulum (ER) stress–related genes, while eHCC started to express oncogenes. Furthermore, integrative analysis indicated that expression of the serine peptidase inhibitor, Kazal type 1 (SPINK1), played a pivotal role in eHCC development. Significant demethylation of SPINK1 was observed in eHCC compared to HGDN. The study also demonstrated that ER stress may induce SPINK1 demethylation and expression in liver cancer cells. In conclusion, these results reveal the dynamics of multiomic aberrations during malignant conversion of liver cancer, thus providing novel pathobiological insights into hepatocarcinogenesis. Multiomics profiling and integrative analyses of stepwise hepatocarcinogenesis reveal novel mechanistic and clinical insights into hepatocarcinogenesis.