Abstract
A novel two-step bioinformatics strategy was applied for identification of signatures with therapeutic implications in hepatitis-associated HCC. Transcriptional profiles from HBV- and HCV-associated HCC samples were compared with non-tumor liver controls. Resulting HCC modulated genes were subsequently compared with different non-tumor tissue samples. Two related signatures were identified, namely “HCC-associated” and “HCC-specific”. Expression data were validated by RNA-Seq analysis carried out on unrelated HCC samples and protein expression was confirmed according to The Human Protein Atlas" (http://proteinatlas.org/), a public repository of immunohistochemistry data. Among all, aldo-keto reductase family 1 member B10, and IGF2 mRNA-binding protein 3 were found strictly HCC-specific with no expression in 18/20 normal tissues. Target peptides for vaccine design were predicted for both proteins associated with the most prevalent HLA-class I and II alleles. The described novel strategy showed to be feasible for identification of HCC-specific proteins as highly potential target for HCC immunotherapy.
Highlights
Regardless the etiology, the overall prognosis for HCC patients is poor with a median survival of 14 months and less than 5% of symptomatic patients surviving more than 2 years[1,2]
Genes included in the “HCC-specific” signature were fully validated by RNA-Seq analysis on unrelated HCC samples and their protein expression was confirmed by interrogating the “The Human Protein Atlas”
Genes differentially modulated were used for subsequent comparison including a broad spectrum of samples from 41 different normal tissue types
Summary
Regardless the etiology, the overall prognosis for HCC patients is poor with a median survival of 14 months and less than 5% of symptomatic patients surviving more than 2 years[1,2]. In the present study the analysis was designed to identify genes over-expressed in HCC tumor lesions as compared to several non-tumor tissue types. This would lead to discovery of potential HCC-specific targets for immunotherapy with minimal residual chance of toxicity. The “liver-specific” signature, including genes upregulated in both HCC and normal liver samples as compared to all other non-tumor tissue types. The “HCC-associated” pathogenetic signature, including genes upregulated in HCC tumor lesions as compared to non-tumor liver samples and the majority of non-tumor tissue types. The “HCC-specific” signature, a subset of the “HCC-associated” signature that included genes uniquely upregulated in HCC tumor lesions as compared to all non-tumor liver samples and non-tumor tissue types. Potential target peptides for vaccine design were predicted for both proteins associated with the most prevalent HLA-class I and II alleles
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