Abstract:

Objective

To investigate the expression level of FMNL3 in hepatocellular carcinoma （HCC） and its relationship with clinicopathological features and prognosis of liver transplant recipients with HCC.

Methods

The clinical data of recipients who underwent liver transplantation for liver cancer and were diagnosed as HCC by histopathology from January 2014 to December 2020 in the Organ Transplantation Center of the Affiliated Hospital of Qingdao University were retrospectively analyzed. Double Immunohistochemical staining was used to detect the expression of FMNL3 in 93 recipients and 56 cases of paracancerous tissues. The clinicopathological characteristics of recipients were collected. Survival curves were plotted by Kaplan-Meier method， and log-rank test was used to compare survival between groups. Cox regression models were used to analyze the risk factors of the prognosis of HCC liver transplant recipients. P＜0.05 was considered statistically significant.

Results

FMNL3 was highly expressed in 57 of 93 HCC tissues （61.3%） and 7 of 56 paracancerous tissues （12.5%）. The expression rate of FMNL3 in HCC tissues was higher than that in paracancerous tissues， and the difference was statistically significant （χ²=33.957， P＜0.05）. Recipients with hepatic capsular invasion， microvascular invasion （MVI）， and vascular tumor thrombus had higher proportions of high FMNL3 expression in HCC tissues than recipients without the above pathological features （χ²=4.890， 4.115， and 8.114， P＜0.05 for all）. As of December 31， 2022， 93 recipients were followed up for a median of 44.9 months （2.7-104.7 months）， with 37 cases of postoperative recurrence and 30 cases of death. Kaplan-Meier survival analysis showed that the 1 -， 3-and 5-year disease-free survival rates （PFS） were 66.7%， 56.1%， 42.8% and 88.9%， 83.3%， 80.2%， and the 1 -， 3-and 5-year overall survival were 80.6%， 68.1%， 53.0%， and 94.4%， 86.1%， 81.6% in the high and low FMNL3 expression groups， respectively， and the differences were statistically significant （χ²=10.494 and 6.994， P＜0.05）. Cox regression analysis showed that FMNL3 expression （HR=2.567， 95%CI：1.070-6.157）， maximum tumor diameter （HR=2.342， 95%CI：1.043-5.260）， preoperative alpha fetoprotein level （HR=0.325， 95%CI：0.127-0.832）， hepatic capsule invasion （HR=3.660， 95%CI：1.496-8.957）， MVI （HR=8.190， 95%CI：2.639-25.422） and vascular tumor thrombus （HR=2.566， 95%CI：1.130-5.829） were independent risk factors affecting postoperative PFS in HCC liver transplant recipients （P＜0.05 for all）.

Conclusions

The expression of FMNL3 in HCC is higher than that in paracancerous tissues， and the expression of FMNL3 in HCC is closely related to hepatic capsular invasion， MVI and vascular tumor thrombus. HCC liver transplant recipients with high FMNL3 expression in HCC tissues had lower PFS and overall survival after transplantation， and FMNL3 expression was an independent risk factor affecting the PFS of HCC liver transplant recipients after transplantation.

Key words: FMNL3, Hepatocellular carcinoma, Liver transplantation, Prognosis, Immunohistochemistry