Correlation Of KIFC1 Expression With Progression And Poor Prognosis Of Hepatocellular Carcinoma

Background and Purposes:Hepatocellular carcinoma(HCC)is a life-threatening malignancy that occurs worldwide;250,000-1,000,000 new cases are diagnosed each year worldwide and the life expectancy from the time of diagnosis is ~6 months.Currently,Hepatectomy and liver transplantation are potentially curative approaches in HCC,but its high relapse characteristics limit the effectiveness of surgical methods to a large extent,and a considerable number of patients are no longer suitable for surgery when diagnosed.Therefore,it is necessary to investigate the genes responsible for the development and progression,and identify new prognostic biomarkers and therapeutic targets in HCC.KIFC1(kinesin family member C1),is a minus end-directed motor protein with a critical role in centrosome clustering in cancer cells.Previous studies have proved that KIFC1 is upregulated in ovarian cancer,breast cancer and non-small cell lung cancer,and it facilitates cancer initiation and progression.However,the expression of KIFC1 and its mechanism in HCC has not been investigated.Accordingly,the present study examined the expression of KIFC1 in HCC via immunohistochemistry,and assessed the expression of KIFC1 in HCC specimens,in terms of its association with HCC clinicopathological characteristics and tumor-free survival rates of patients.Furthermore,the effects of KIFC1 knockdown on the regulation of HCC cell malignant behaviors were examined in vitro.Methods:1.We investigated the expression of KIFC1 in paired hepatocellular carcinoma(HCC)tissues and adjacent non-cancerous tissues from 91 patients and assessed the expression of KIFC1 in HCC specimens,in terms of its association with HCC clinicopathological characteristics.2.Western Blot was used to investigate the expression of KIFC1 protein in MHCC-97 H,SMMC-7721,HCC-LM3 and HL-7702 cells.3.The proliferation,cycle,apoptosis,migration and invasion of HCC cells were detected by CCK-8,Transwell and flow cytometry when KIFC1 knockdown.Results:1.KIFC1 was expressed at high levels in HCC tissues,compared with the peritumoral tissues(54.9,vs.14.3%,P < 0.01).Specifically,a high level of KIFC1 was significantly associated with tumor emboli(P = 0.033),metastasis(P = 0.001),recurrence(P = 0.015)and time of recurrence(P = 0.015).The Kaplan-Meier analysis showed that the expression of KIFC1 was significantly associated with tumor-free survival rate(P = 0.004).Cox proportional hazards regression model showed that KIFC1 is an independent prognostic factor of HCC patients(HR = 0.518;95%CI = 0.281-0.953;P = 0.035).The GEPIA database showed that KIFC1 mRNA was highly expressed in the HCC tissue(P < 0.05)and the mRNA expression of KIFC1 was significantly associated with disease-free survival rate(P = 0.00064)and overall survival rate(P = 1.9e-05).2.The expression of KIFC1 was high in MHCC-97 H,SMMC-7721 and HCC-LM3 cells,but was absent in HL-7702 cells.3.When KIFC1 knockdown,the proliferation,migration and invasion ability of HCC cells decreased,but the apoptosis rate increased.At the same time,the apoptosis related proteins(Bcl-2,BAX and P53)and EMT(epithelial-mesenchymal transition)related proteins(E-cadherin,N-cadherin,MMP-2,β-catenin,slug and zeb1)in HCC cells also changed correspondingly.Conclusion:KIFC1 is highly expressed in HCC and involved in the development of HCC.It is expected to become a potential therapeutic target and prognostic marker for HCC.