Liver cancer ranks high among cancer death rates and is resistant to most therapies. Studies of protein functionality are limited in patients with hepatocellular carcinoma (HCC). Here, we constructed an HCC kinome activity atlas and used it to develop personalized medicine technology applicable to profiling protein functionality. We used PamGene PamStation kinome technology that quantified protein kinase activity across hundreds of pathways for HCC tumor and non-tumor regions from both sexes. According to our bioinformatic analyses of kinases, ABL was the most active for men and women with HCC. Next, we employed three ABL inhibitors while running the PamStation, which revealed discernible alterations in ABL and other pathways. We deconvoluted over 500 kinase pathways and generated a personalized medicine (PerMed) score delineating activity levels; results were substantiated in five human hepatocyte cancer cell lines. Our work establishes an HCC kinome atlas and demonstrates PamStation’s potential for precision medicine applications.

Z.A.K., E.A.B., and T.D.H.J. submitted a utility patent for personalized medicine use on this work. The other authors declare no competing interests.

This work was supported by grants from the National Institutes of Health (NIH) R01DK121797 (T.D.H.J.), R01DA058933 (T.D.H.J.), R01HL174521 (T.D.H.J.), F31HL170972 (Z.A.K.), F31HL175979 (E.A.B.), and American Heart Association (AHA) grant 25PRE1374495 (G.J.M.). The HCC and normal adjacent tissue were received from and supported by the Biospecimen Procurement & Translational Pathology Shared Resource Facility of the University of Kentucky Markey Cancer Center (P30CA177558).

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Human liver biopsies of hepatocellular carcinoma and normal adjacent tissue were received from the Biospecimen Procurement & Translational Pathology Shared Resource Facility (BPTP SRF) of the University of Kentucky Markey Cancer Center (P30CA177558). The samples were deidentified to the research group and designated non-human research with IRB exemption. The Institutional Review Board (IRB) at the University of Kentucky waived ethical approval for this work.

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