The protein phosphatase, Mg2+/Mn2+ dependent, 1E (PPM1E) inactivates multiple substrates including 5'-AMP activate protein kinases (AMPK) which inhibits the growth and survival of cancer cells. However, no study on the possible genetic association of PPM1E single nucleotide polymorphism (SNP) with HCC has been conducted yet.

HCC patients (153 males and 30 females) and healthy individuals (167 males and 224 females) were enrolled in this study. We selected three exonic SNPs (rs16943333, rs3809724 and rs3809723) in the 3'- UTR of the PPM1E gene.

rs16943333, rs3809724 and rs3809723 of PPM1E were not significant differences between the HCC group and the control group. In the further analysis, we divided HCC patients into two groups according to tumor size, serum AFP level, UICC stage, radiologic morphology and portal vein thrombosis. We found that rs16943333 and rs3809724 in PPM1E were significantly associated with the tumor size. The genotype frequency of rs16943333 was associated with tumor size in the codominant 2 (G/G vs. A/A, p=0.038, Fisher's exact p=0.06, OR=6.27, 95% CI=1.11-35.41), dominant (G/G / G/A vs. A/A, p=0.014, OR=2.27, 95% CI=1.17-4.41) and log-additive models (p=0.0058, OR-2.16, 95% CI=1.23-3.79). In the allele frequency analysis, rs16943333 was associated with tumor size (p=0.010, OR=2.07, 95% CI=1.19-3.59). The genotype frequency of rs3809724 was associated with tumor size in the codominant 2 (C/C vs. T/T, p=0.030, Fisher's exact p=0.09, OR=5.31, 95% CI=1.17-24.05), dominant (C/C / C/T vs. T/T, p=0.030, OR=2.04, 95% CI=1.07-3.89) and log-additive models (p=0.011, OR-1.97, 95% CI=1.16-3.37). In the allele frequency analysis, rs3809724 was associated with tumor size (p=0.023, OR=1.84, 95% CI=1.09-3.12).

Our results indicated that when we perform liver transplantation for HCC, sufficient evaluation and careful selection by genetic marker are required.

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