Expression of hnRNPK & Claudin-4 in HCV-Induced Early HCC and Adjacent Liver Tissue

HCC in Egypt usually occurs in HCV cirrhotic livers with poor prognosis due to late diagnosis. High hnRNPK & low Claudin-4 profiles indicate Epithelial Mesenchymal Transition (EMT), malignant transformation and high-grade tumours.

We studied the immunohistochemical expression of hnRNPK and Claudin-4 in HCV induced early HCC (eHCC) and adjacent liver tissue in Egyptian patients to improve eHCC detection in cirrhotic livers with better curative therapy options.

We studied the immunohistochemical expression of hnRNPK and Claudin-4 in 100 Egyptian patients resection specimens of HCV induced early HCC (eHCC) and adjacent liver tissue, in order to improve eHCC detection in cirrhotic livers, thus improving their therapeutic options.

Early HCC grade significantly directly correlated with nuclear hnRNPK/5HPFs count and inversely correlated with Claudin-4 expression %, with a converse correlation between hnRNPK and Claudin-4. Moreover in eHCC, combined hnRNPK ≥ 30/5HPFs & Claudin-4 ≥ 40% significantly distinguished low grade eHCC (G1) from high grade eHCC (G2&G3), with sensitivity 97% & specificity 69.7% for hnRNPK ≥ 30/5HPFs, and with sensitivity 70% & specificity 94.3% for Claudin-4 ≥ 40%. Moreover in the adjacent liver, both markers expressions significantly directly correlated with each other and with METAVIR fibrosis score but not with activity. Furthermore, 58% of eHCCs showed hnRNPK ≥ 30 Claudin-4 < 40% profile, indicating EMT type 3, compared to 26% with hnRNPK ≥ 30 Claudin-4 ≤ 10% profile in adjacent cirrhotic/ precirrhotic liver, with significant use of combined hnRNPK ≥ 30/5HPFs & Claudin 4 ≤ 10% as eHCC prediction cut offs in cirrhosis (p < 0.05).

Combination of hnRNPK and Claudin-4 can indicate early HCC development in HCV cirrhotic livers using hnRNPK ≥ 30/5HPFs & Claudin-4 ≤ 10% cut offs. Also, combination of hnRNPK ≥ 30/5HPFs & Claudin-4 ≥ 40% can distinguish low grade eHCC (G1) from high grade eHCC (G2&G3).