Deep View of HCC Gene Expression Signatures and Their Comparison with Other Cancers

Abstract

Background: Gene expression signatures correlate genetic alterations with specific clinical features, providing the potential for clinical usage. A plethora of HCC-dependent gene signatures have been developed in the last two decades. However, none of them has made its way into clinical practice. Thus, we investigated the specificity of public gene signatures to HCC by establishing a comparative transcriptomic analysis, as this may be essential for clinical applications. Methods: We collected 10 public HCC gene signatures and evaluated them by utilizing four different (commercial and non-commercial) gene expression profile comparison tools: Oncomine Premium, SigCom LINCS, ProfileChaser (modified version), and GENEVA, which can assign similar pre-analyzed profiles of patients with tumors or cancer cell lines to our gene signatures of interests. Among the query results of each tool, different cancer entities were screened. In addition, seven breast and colorectal cancer gene signatures were included in order to further challenge tumor specificity of gene expression signatures. Results: Although the specificity of the evaluated HCC gene signatures varied considerably, none of the gene signatures showed strict specificity to HCC. All gene signatures exhibited potential significant specificity to other cancers, particularly for colorectal and breast cancer. Since signature specificity proved challenging, we furthermore investigated common core genes and overlapping enriched pathways among all gene signatures, which, however, showed no or only very little overlap, respectively. Conclusion: Our study demonstrates that specificity, independent validation, and clinical use of HCC genetic signatures solely relying on gene expression remains challenging. Furthermore, our work made clear that standards in signature generation and statistical methods but potentially also in tissue preparation are urgently needed.

Pan-Cancer Analysis Reveals Disulfidoptosis-Associated Genes as Promising Immunotherapeutic Targets: Insights Gained from Bulk Omics and Single-Cell Sequencing Validation

“…Among our investigations into hepatocellular carcinoma, single-cell sequencing was notably significant. This advanced approach allowed us to dissect the cellular milieu of HCC and unveil the complicated cellular heterogeneity that often remains concealed in bulk RNA sequencing [34].…”

Current Trends and Advancements in the Management of Hepatocellular Carcinoma

“…As a result, up to now none of those signatures has made it into clinical routine decision making [42]. Furthermore, recent data on a high rate of positive signatures among randomly selected gene signatures [43] and many signatures being of potential use in other cancers as well [44] raised concerns about the specificity of these signatures and the general approach itself [42].…”

Novel hepatocellular carcinomas (HCC) Subtype-Specific Biomarkers

“…Liver cancer, particularly HCCs, frequently emerges due to chronic factors such as cirrhosis triggered by hepatitis B or C, leading to its high incidence [25][26][27][28][29]42,43]. Viral-induced gene expression changes across DNA, RNA, and protein levels have been observed in HCC [44][45][46][47][48][49][50][51], emphasizing the significance of transcription factors (TFs) in liver cancer development. Therefore, a key aim of this study is to identify the TFs linked to potential diagnostic and prognostic biomarkers in HCC.…”

“…CC-BY-NC-ND 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made [44][45][46][47][48][49][50][51][52]. The rapid expansion of HCC data repositories is anticipated to continue, continually enhancing the existing pool of diagnostic and prognostic biomarkers in the currently underserved domain of liver cancer research.…”