Given evidence that O-β-GlcNAc at Ser204 reduces IGF-II binding by IGFBP-6, PTM-aware assays (e.g., glyco-specific enrichment coupled to targeted MS) are warranted to test whether modified IGFBP-6 better stratifies virally driven HCC or predicts IGF-pathway activity than total IGFBP-6 alone [64]. Here, IGF2 is linked to hepatocellular carcinoma.