BackgroundKIF18A is associated with a variety of tumours; however, the specific mechanism of action of KIF18A in hepatocellular carcinoma (HCC) remains unclear. In this study, in vitro and in vivo experiments were performed with the aim of exploring the potential function and molecular mechanism of kinesin KIF18A in the occurrence and development of HCC.MethodsWe detected the expression of KIF18A in tumour and adjacent tissues as well as cell proliferation, cell invasion and migration in hepatoma cells after silencing KIF18A. KIF18A-silenced hepatoma cells were subcutaneously injected into nude mice to verify the tumorigenicity of KIF18A. We also detected the expression of signal pathway-related proteins in hepatoma cells after KIF18A knockdown with the aim of exploring the association between KIF18A and related signalling pathways.ResultsThe level of KIF18A protein was higher in liver cancer tissues than adjacent tissues. After silencing KIF18A in SMMC-7721 and HepG2 cells, cell growth was obviously inhibited; the migration and invasion abilities were significantly decreased and the in vivo tumour weight was decreased compared to the control group (0.201 ± 0.088 g vs 0.476 ± 0.126 g, p = 0.009). The expression of cell cycle-related protein (cyclin B1), invasion and metastasis-related proteins (MMP-7 and MMP-9) and Akt-related proteins in hepatoma cells was also decreased after knocking down KIF18A.ConclusionsKIF18A may promote proliferation, invasion and metastasis of HCC cells by promoting the cell cycle signalling pathway as well as the Akt and MMP-7/MMP-9-related signalling pathways and may serve as a new target for the diagnosis and treatment of HCC.

Previous cDNA microarray experiments revealed that the ATP-dependent DNA helicase Q4 (RECQL4) gene is overexpressed in hepatocellular carcinoma (HCC) tissues. However, the exact role of RECQL4 in HCC remains unknown. The present study aimed to investigate RECQL4 expression in HCC and to analyze the potential clinical implications of RECQL4 expression in HCC patients. The expression of RECQL4 mRNA was assessed in 205 samples of HCC tissues by reverse transcription-quantitative polymerase chain reaction. The results demonstrated that the expression of RECQL4 mRNA in HCC tissues was significantly higher compared with adjacent normal liver tissues (P<0.001). The level of RECQL4 mRNA expression was associated with high a-fetoprotein (AFP) levels (>100 ng/ml), tumor size (>6 cm), and Barcelona Clinic Liver Cancer stage (all P<0.05). Kaplan-Meier survival analysis indicated that HCC patients with higher levels of RECQL4 expression exhibited significantly shorter disease-free survival (DFS) and overall survival (OS) times compared with those with low levels of expression. Multivariate survival analysis revealed that high RECQL4 expression was a significant independent predictor for DFS [HR, 1.635; 95% confidence interval (CI), 1.062–2.515; P=0.025] and OS (HR, 1.618; 95% CI, 1.050–2.493; P=0.029) of HCC patients. These data indicated that RECQL4 might be a novel diagnostic and prognostic biomarker for HCC patients.

Background: Currently, there is still a lack of effective biomarkers for the recurrence monitoring and survival prognosis assessment of hepatocellular carcinoma (HCC) patients with alpha-fetoprotein (AFP)-negative (≤20 ng/mL) after radical resection. Methods: The clinicopathological data of 606 patients (303 in the AFP-negative group and 303 in the AFP-positive group) who underwent radical resection of HCC were analyzed retrospectively. Results: The gamma-glutamyl transpeptidase to lymphocyte count ratio (GLR) of patients in the AFP-negative group was lower than that in the AFP-positive group (p <0.001). The GLR level of the early-recurrence group was higher than that of the non-early-recurrence group (p =0.003). GLR had fair accuracy in predicting the early-recurrence of HCC patients [c-index=0.654 (95% CI=0.606-0.702); AUC=0.681 (95% CI=0.625-0.733)]. Univariate analysis showed that patients with tumor size <5 cm, no microvascular invasion, single tumor, no metastasis, BCLC stage 0-A, no recurrence, and GLR ≤45.0 had longer disease-free survival (DFS) and overall survival (OS) among AFP-negative HCC patients. In addition, multivariate Cox proportional hazards regression analysis showed that tumor size <5 cm (p =0.003), no recurrence (p <0.001), and GLR <45.0 (p <0.001) were independent predictors of longer OS. Conclusion: GLR may be a potential indicator for early recurrence monitoring and prognosis evaluation in HCC patients with AFP-negative after radical resection.

Clinical outcomes of patients with hepatocellular carcinoma (HCC) are highly variable. This study aims to identify and validate a simple, readily available, and objective prognostic index for the management of HCC. Data from 724 HCC patients undergoing curative resection were evaluated and randomly divided into two cohorts for building and validating the prognostic index. A best model, NγLR = (neutrophil count [109/L] × γ-glutamyl transpeptidase [U/L]) /(lymphocyte count [109/L] × U/L), was selected. An optimal cut-off value of 103.6 for NγLR stratified patients into high NγLR (>103.6) and low NγLR (≤103.6) groups. NγLR > 103.6 was closely associated with HCC malignant characteristics. Elevated NγLR predicted a worse overall survival (OS) and progression-free survival (PFS) for HCC patients and remained an independent predictor for both types of survival. Moreover, early recurrence rates in patients with NγLR > 103.6 were higher than that in patients with NγLR ≤ 103.6 (P < 0.0001). NγLR was an important independent predictor of survival for HCC patients and might be a new promising method to identify patients at different risks of early recurrence and survival after curative resection.

BackgroundAt present, the predictive ability of the prognostic indicator of hepatocellular carcinoma (HCC) is still limited. This study aims to analyze the relationship between the preoperative high-sensitivity C-reactive protein to lymphocyte ratio (HCLR) and the clinicopathologic characteristics of HCC.Patients and methodsA total of 229 HCC patients undergoing surgical resection were retrospectively analyzed. The majority of the patients (132/229) had tumors larger than 5 cm, and 45 out of 229 had more than one tumor focus. Receiver operating characteristic curve analysis was used to decide the cutoff value of HCLR. The overall survival (OS) and progression-free survival (PFS) rates were evaluated by adopting the Kaplan–Meier method.ResultsThe cutoff value of HCLR for the best discrimination of HCC prognosis was 1.3 with a sensitivity of 75.5% and a specificity of 71.8%. The area under the receiver operating characteristic curve was 0.791 (95% CI, 0.731–0.840). Preoperative HCLR at a high level (>1.3) was positively correlated with large tumor size, TNM stage, microvascular invasion, and recurrence. The mean OS and PFS in patients with HCLR >1.3 were significantly shorter than in those with HCLR ≤1.3. Univariate and multivariate analyses revealed the HCLR was an independent predictor of OS and PFS.ConclusionHCLR was an important independent predictor of dismal prognosis in HCC patients and can be used as a sensitive indicator for the dynamic monitoring of postoperative patients.