P53 Inducible Gene-3: Potential Serum Marker for Hepatocellular Carcinoma Beyond Milan Criteria

Mamatha Bhat, Samara Goldstein, Jean Tchervenkov, Safiyya Ali, Amy Neville, Syamala Kalyanasundaram, Shuqing Liu, Minh-Tri Nguyen, Prosanto Chaudhury, Mazen Hassanain, Peter Ghali, Peter Metrakos


Aims: The diagnosis of Hepatocellular carcinoma (HCC) is usually made late, precluding curative resection or liver transplantation in over 70% of HCC patients. P53 inducible gene 3 (PIG3) is a p53 downstream gene and a key component of the DNA damage response pathway, which is relevant in conditions with rapid cell turnover such as HCC. Our aim was to assess whether PIG3 could serve as a novel biomarker for HCC. Methods: A pilot study of 37 consecutive patients with the diagnosis of HCC, 42 patients with hepatic cirrhosis versus healthy controlswas conducted. Serum AFP and PIG3 levels measured with enzyme-linked immunosorbent assay were compared across groups using student t-testand correlation coefficient (R) between AFP and PIG3 was calculated. Results: Clinical characteristics were similar across the HCC and cirrhosis groups. Serum PIG3 levels were significantly higher among patients with cirrhosis or HCC (23.27 ± 13.26 and 24.1 ± 18.61 ng/mL, respectively), as compared to healthy controls (3.71 ± 1.79 ng/mL, p<0.0001). PIG3 values were significantly different across the following tumor diameter ranges: less than 2 cm, 18.47 ng/mL; 2 to 5 cm, 18.54 ng/mL; and greater than 5 cm, 38.72 ng/mL; p=0.0012. The correlation coefficient between log (AFP) and PIG3 levels in HCC patients was r=0.4564, p=0.005. Conclusion: Serum p53-inducible gene 3 levels were significantly elevated in patients with HCC beyond 5 cm, indicating potential as an adjunct to imaging in determining eligibility for liver transplantation. The potential for PIG3 as a biomarker of HCC warrants further prospective study.


p53 inducible gene; Hepatocellular carcinoma; Milan criteria; Serum marker

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