High spindle and kinetochore-associated complex subunit-3 expression predicts poor prognosis and correlates with adverse immune infiltration in hepatocellular carcinoma

BACKGROUND Spindle and kinetochore-associated complex subunit 3(SKA3)is a malignancyassociated gene that plays a critical role in the regulation of chromosome separation and cell division.However,the molecular mechanism through which SKA3 regulates tumor cell proliferation in hepatocellular carcinoma(HCC)has not been fully elucidated.AIM To investigate the molecular mechanisms underlying the role of SKA3 in HCC.METHODS SKA3 expression,clinicopathological,and survival analyses were performed using multiple public database platforms,and the results were verified by Western blot and immunohistochemistry staining using collected clinical samples.Functional enrichment analyses were performed to evaluate the biological functions and molecular mechanisms of SKA3 in HCC.Furthermore,the Tumor Immune Estimation Resource and single-sample Gene Set Enrichment Analysis(ssGSEA)algorithms were utilized to investigate the abundance of tumor-infiltrating immune cells in HCC.The response to chemotherapeutic drugs was evaluated by the R package“pRRophetic”.RESULTS We found that upregulated SKA3 expression was significantly correlated with poor prognosis in patients with HCC.Multivariable Cox regression analysis indicated that SKA3 was an independent risk factor for survival.GSEA revealed that SKA3 expression may facilitate proliferation and migratory processes by regulating the cell cycle and DNA repair.Moreover,patients with high SKA3 expression had significantly decreased ratios of CD8+T cells,natural killer cells,and dendritic cells.Drug sensitivity analysis showed that the high SKA3 group was more sensitive to sorafenib,sunitinib,paclitaxel,doxorubicin,gemcitabine,and vx-680.CONCLUSION High SKA3 expression led to poor prognosis in patients with HCC by enhancing HCC proliferation and repressing immune cell infiltration surrounding HCC.SKA3 may be used as a biomarker for poor prognosis and as a therapeutic target in HCC.

Three-dimensional morphometric analysis for hepatectomy of centrally located hepatocellular carcinoma:A pilot study

AIM: To describe a three-dimensional model(3DM) to accurately reconstruct anatomic relationships of centrally located hepatocellular carcinomas(HCCs).METHODS: From March 2013 to July 2014, reconstructions and visual simulations of centrally located HCCs were performed in 39 patients using a 3D subject-based computed tomography(CT) model with customdeveloped software. CT images were used for the 3D reconstruction of Couinaud's pedicles and hepatic veins, and the calculation of corresponding tumor territories and hepatic segments was performed using Yorktal DMIT software. The respective volume, surgical margin, and simulated virtual resection of tumors were also estimated by this model preoperatively. All patients were treated surgically and the results were retrospectively assessed. Clinical characteristics, imaging data, procedure variables, pathologic features, and postoperative data were recorded and compared to determine the reliability of the model.RESULTS: 3D reconstruction allowed stereoscopic identification of the spatial relationships between physiologic and pathologic structures, and offered quantifiable liver resection proposals based on individualized liver anatomy. The predicted values were consistent with the actual values for tumor mass volume(82.4 ± 109.1 m L vs 84.1 ± 108.9 m L, P = 0.910), surgical margin(10.1 ± 6.2 mm vs 9.1 ± 5.9 mm, P = 0.488), and maximum tumor diameter(4.61 ± 2.16 cm vs 4.53 ± 2.14 cm, P = 0.871). In addition,the number and extent of portal venous ramifications, as well as their relation to hepatic veins, were visualized. Preoperative planning based on simulated resection facilitated complete resection of large tumors located in the confluence of major vessels. And most of the predicted data were correlated with intraoperative findings.CONCLUSION: This 3DM provides quantitative morphometry of tumor masses and a stereo-relationship with adjacent structures, thus providing a promising technique for the management of centrally located HCCs.

Management of centrally located hepatocellular carcinoma:Update 2016

Centrally located hepatocellular carcinoma(HCC)is sited in the central part of the liver and adjacent to main hepatic vascular structures.This special location is associated with an increase in the difficulty of surgery,aggregation of the recurrence disease,and greater challenge in disease management.This review summarizes the evolution of our understanding for centrally located HCC and discusses the development of treatment strategies,surgical approaches and recurrence prevention methods.To improve patient survival,a multi-disciplinary modality is greatly needed throughout the whole treatment period.

Hepatocellular adenoma with malignant transformation in male patients with non-cirrhotic livers

Introduction:Hepatocellular adenomas(HCAs),with a risk of malignant transformation into hepatocellular carcinoma(HCQ,classically develop in young women who are taking oral contraceptives.It is now clear that HCAs may also occur in men.However,it is rarely reported that HCAs with malignant transformation occur in male patients with non-cirrhotic livers.This study aimed to characterize the malignancy of HCAs occurring in male patients.Methods:All patients with HCAs with malignant transformation who underwent hepatectomy at the Cancer Institute and Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College between January 1,1999 and December 31,2011 were enrolled in the study.The clinical characteristics as well as radiologic and pathologic data were reviewed.Results:HCAs with malignant transformation were observed in 5 male patients with non-cirrhotic livers,but not in female patients.The alpha-fetoprotein(AFP) levels were higher in patients with HCAs with malignant transformation than in patients with HCAs without malignant transformation.The diameters of the tumors with malignant transformation were larger than 5 cm in 3 cases and smaller than 5 cm in 2 cases.The 5 patients were all alive without recurrence by the end of the study period.The disease-free survival times of the 5 patients were 26,48,69,69,and 92 months.Conclusion:Our results indicate that resection would be advised even if the presumptive diagnosis is adenoma smaller than 5 cm in diameter,especially in male patients.

Research progress regarding programmed cell death 1/programmed cell death ligand 1 inhibitors combined with targeted therapy for treating hepatocellular carcinoma

In recent years,a number of targeted therapeutic agents have achieved success in phase III trials in patients with advanced hepatocellular carcinoma(HCC),including sorafenib,lenvatinib,and regorafenib.Immunotherapy is considered to be an effective treatment for advanced HCC.Immune checkpoint inhibitors targeting programmed cell death 1(PD-1)/programmed cell death ligand 1(PDL1)are important antitumor immunotherapy agents that represent breakthroughs in the treatment of advanced HCC.However,treating advanced HCC is still a great challenge,and the need for new treatments remains urgent.This review briefly summarizes the research progress in the use of PD-1/PD-L1 inhibitors combined with targeted therapy for treating HCC.