To investigate the predictive value of YTHDF1 single nucleotide polymorphism (SNP) in the hepatocellular carcinoma recurrence of liver transplant recipients within Hangzhou criteria.

We retrospectively analyzed the clinical data of 139 recipients who received liver transplantation from the First Affiliated Hospital of Zhejiang University and met Hangzhou criteria from January 1, 2015 to May 31, 2019, with a median age of 54 years (30-73 years), including 120 males and 19 females. The tag SNPs (Han population, minor allele frequency>5% and r²>0.8) were obtained from 1 000 Genmoes Project database with Haploview. Paired-sample Wilcoxon test was used to compare the expression differences of YTHDF1 in liver cancer and adjacent tissues. Kaplan-Meier method was used to draw recurrence-free survival curves of rs68041888 G-carrying and non-carrying liver recipients and to compare recurrence-free survival time. Cox proportional hazards regression model was used to analyze the factors affecting tumor recurrence after liver transplantation. The Chi-square test or Fisher′s exact probability method was used to compare the YTHDF1 tagSNP genotype distribution of the tumor recurrence and non-recurrence groups. A P<0.05 was considered statistically significant.

Follow-up to May 31, 2020, the average recurrence-free survival time of 139 liver transplant recipients was (43.9±2.0) months (1 to 56 months). Among 139 liver recipients, 28 had recurrence. The expression level of YTHDF1 in liver cancer tissues is higher than that in adjacent tissues (6 points vs. 3 points, Z=4.087, P<0.05). There were 8, 13 and 7 cases of G/A, G/G and A/A at rs68041888 locus among 28 recipients in recurrence group, respectively. Among the 111 recipients in the non-recurrence group, they were 42, 61, and 8, respectively. The difference in genotype distribution between the two groups was statistically significant (χ²=0.025, P<0.05). There was no statistically significant difference in the distribution of other tagSNP genotypes (all P>0.05). rs68041888 G non-carrying type (locus type A/A) recipients of liver cancer recurrence rate (46.7%, 7/15) is higher than that of carrier type (locating type G/A, G/G type) (16.9%, 21/124) (P=0.018). The 1-year recurrence-free survival rates of rs68041888 G-carrying and non-carrying recipients were 87.1% (108/124) and 66.7% (10/15), respectively, and the recurrence-free survival time was (45.6±2.1) and (27.9±5.2) months (χ²=5.980, P=0.014). The proportions of recipients with preoperative AFP≤400 μg/L and rs68041888 G-carrying type in the recurrence group were 71.4% (20/28) and 75.0% (21/28), respectively, which were lower than those in the non-recurrence group [91.0% (101/111), 92.8% (103/111)] (χ²=5.955 and 5.621, both P<0.05). The differences in other indicators were not statistically significant (all P>0.05). The variables with P<0.10 in the univariate analysis were incorporated into the Cox proportional hazards regression model for multivariate analysis. The results showed that preoperative AFP, tumor number, histological grade and rs68041888 G carrying or not were related to tumor recurrence (RR=5.024, 2.352, 2.523, 3.693, P all<0.05).

The liver recipients who met Hangzhou criteria without rs68041888 G type have a higher risk of recurrence. The rs68041888 genotype has potential value in predicting the recurrence of HCC after liver transplantation.