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

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.

Difference in Cell Characteristics among the Monoclonal Cell Populations Obtained from the Human Umbilical Cord Blood Derived Mesenchymal Stem Cell Population / 대한정형외과학회잡지

PURPOSE: The aim of this study was to obtain single cell-derived clones from human umbilical cord blood (hUCB) derived mesenchymal stem cell (MSC) population, to compare the gene expression patterns and differentiation characteristics among the hUCB derived MSC population and its monoclonal cell populations, and to determine if the MSC population is homogenous. MATERIALS AND METHODS: The single cells were isolated from a hUCB derived MSC population and cultured on each well of a culture plate. The gene expression pattern of each monoclonal cell population expanded from the single cells was detected by RT-PCR for osteogenic, chondrogenic, and adipogenic specific genes. The monoclonal cell populations were differentiated into osteogenic, chondrogenic, and adipogenic lineages and were confirmed by specific staining. RESULTS: Fifteen monoclonal cell populations were obtained from the total seeding of 864 single cells. The cell morphology and gene expression patterns among the hUCB derived MSCs and its monoclonal cell population were different. Tri-lineage differentiation potency was different among the monoclonal cell populations. CONCLUSION: The difference in the cell morphology, gene expression patterns, and differentiation characteristics among the monoclonal cell populations suggest heterogeneity of the MSC population isolated using the currently available method.

Difference in HLA-DR Expression of Human Umbilical Cord Blood Derived Mesenchymal Stem Cells after Tri-lineage Differentiation / 대한정형외과연구학회지

PURPOSE: The aim of this study was to examine the expression of HLA-DR surface antigen in undifferentiated human umbilical cord blood (hUCB) derived mesenchymal stem cells (MSCs) and after osteogenic, chondrogenic, and adipogenic differentiation. MATERIALS AND METHODS: hUCB-derived MSCs were differentiated into osteogenic, chondrogenic, and adipogenic lineages. Differentiation was assessed by immunohistochemical staining and RT-PCR. The expression of HLA-DR was assessed with antihuman HLA-DR antibody in undifferentiated hUCB-derived MSCs and after tri-lineage differentiation. RESULTS: HLA-DR expression was negative in undifferentiated hUCB-derived MSCs and after osteogenic and adipogenic differentiation. However, HLA-DR surface antigen was expressed after chondrogenic differentiation. CONCLUSION: The immunologic properties of hUCB-derived MSCs differ from known reports on bone marrow derived MSCs from the results of this study. Careful immunological survey seems to be needed in case of considering the transplantation of hUCB-derived MSCs differentiated into chondrocytes or cartilaginous tissue.