Purpose: Studies show that high expression of non-SMC condensin I complex subunit G (NCAPG) is associated with many tumors. In this study, we explore the mechanism by which NCAPG promotes proliferation in hepatocellular carcinoma (HCC). Patients and methods: Liver cancer and paracancerous tissue specimens of 90 HCC patients were collected, and expression levels of NCAPG in these tissues and cell lines were evaluated by Western blotting and immunohistochemistry. HCC cells were transfected with siRNAs and plasmids, and pathway activators or inhibitors were added. The 5-ethynyl-2ʹ-deoxyuridine (EdU) proliferation assay was used to measure cell proliferation. Flow cytometry was used to evaluate cell apoptosis. Western blot assays were performed as a standard procedure to detect total protein expression. Treated HCC cells were subcutaneously injected into nude mice. Results: Analysis using the Oncomine database showed that NCAPG was upregulated in HCC and immunohistochemistry and Western blot assays showed it was upregulated in both HCC tissues and HCC cell lines. The overexpression of NCAPG could promote HCC cell proliferation and reduce HCC cell apoptosis. More importantly, RNA-sequencing analysis predicted that NCAPG plays a role in the HCC via PI3K-AKT signaling pathway. The PI3K/AKT/FOXO4 pathway was aberrantly activated, and the expressions of apoptosis-related protein were altered when NCAPG was overexpressed or silenced both in vitro and in vivo. LY294002, a PI3K inhibitor, could eliminate the NCAPG role of promoting HCC cell proliferation and reducing HCC cell apoptosis, while 740Y-P, a PI3K activator, contributed to the opposite effect. Conclusion: NCAPG functions as an oncogene in HCC and plays a role in promoting cell proliferation and antiapoptosis through activating the PI3K/AKT/FOXO4 pathway.

Background: Although the prognostic outcomes of liver cancer (LC) cases have improved with the advancement in diagnostic technology and treatment methods, the transferability and recurrence of HCC and the 5-year and 10-year survival rates of patients have remained unsatisfactory. As a result, there is a need for more accurate diagnostic indicators that can detect liver cancer early, effectively improving the prognosis of patients. Whole-genome sequencing (WGS) revealed that circ-ZEB1 and PIK3CA are highly expressed in HCC tissues, whereas miR-199a-3p is significantly downregulated in HCC. Multiple databases search and biological analysis revealed that elevated expression of circ-ZEB1 and PIK3CA was related to poor prognosis of HCC. In vitro and in vivo studies revealed that upregulated levels of PIK3CA and circ-ZEB1 were closely associated with HCC proliferation and apoptosis. Based on these results, we believe that circ-ZEB1 and PIK3CA could be used as biomarkers to diagnose and treat patients with HCC. More importantly, circ-ZEB1 can promotes the expression of PIK3CA by silencing miR-199a-3p and affecting the progression of HCC. Methods and results: Postoperative specimens from 56 patients with HCC who had not undergone chemotherapy from 2015 to 2018 were collected from the Department of Hepatobiliary Surgery, Second Affiliated Hospital of Nanchang University. WGS revealed differential expression of genes in HCC. Furthermore, RT-qPCR detected the expression of circ-ZEB1, miR-199a-3p, and PIK3CA in HCC tissues. MTT, EdU, and plate cloning experiments were conducted to detect cell proliferation, whereas flow cytometry analysis was used to detect apoptosis. FISH was used to co-localize circ-ZEB1 and miR-199a-3p, and biotin-coupled probe pull-down assay was used to detect the specific binding of circ-ZEB1 and miR-199a-3p. The dual-luciferase report assay detected the association of miR-199a-3p with PIK3CA. Western blotting was used to study the expression of PIK3CA protein. Circ-ZEB1 and PIK3CA were upregulated in HCC and predicted a poor prognosis. MiR-199a-3p showed low expression in HCC, whereas downregulation of circ-ZEB1 reduced HCC cell proliferation and promoted cell apoptosis. MiR-199a-3p blocked the effect of circ-ZEB1 on HCC. Circ-ZEB1 served as a biomarker of HCC. Circ-ZEB1 promoted the expression of PIK3CA by silencing miR-199a-3p to affect the progress of HCC. Conclusions: Circ-ZEB1 promoted the expression of PIK3CA by depleting miR-199a-3p, thereby affecting HCC proliferation and apoptosis.

The non‑SMC condensin I complex subunit G (NCAPG) that organizes the coiling topology of individual chromatids, represents an overexpressed antigen in various types of cancer, and also contributes to restructuring chromatin into rod‑shaped mitotic chromosomes and ensuring the segregation of sister chromatid during cell division. In this study, we investigated the association between NCAPG expression and the biological behavior of hepatocellular carcinoma (HCC) to further explore the potential of NCAPG as a therapeutic target. The expression of NCAPG was detected in human HCC cell lines and tumor samples. The effects of NCAPG on the cell cycle, apoptosis and metastasis were investigated by various assays. NCAPG was found to be overexpressed in HCC compared with the adjacent normal tissue (P<0.001), and high levels of NCAPG expression were found to significantly correlate with recurrence, the time of recurrence, metastasis, differentiation and TNM stage. Furthermore, an elevated expression of NCAPG was associated with a poor overall survival (P<0.05). In addition, in vitro experiments further confirmed the ex vivo data; i.e., the knockdown of NCAPG expression reduced HCC cell viability, but induced apoptosis and arrested the cells at the S phase of the cell cycle. The knockdown of NCAPG expression also inhibited tumor cell migration and the cell invasive capacity in vitro. At the protein level, the knockdown of NCAPG expression upregulated Bax, cleaved caspase‑3 and E‑cadherin, but downregulated cyclin A1, CDK2, Bcl‑2, N‑cadherin and HOXB9 expression, suggesting that the knockdown of NCAPG expression suppressed tumor cell epithelial‑mesenchymal transition. On the whole, this study demonstrates that NCAPG plays an important role in the development and progression of HCC, and that it may be a novel therapeutic target for patients with HCC.

The purpose of this study was to explore trends in incidence, incidence-based (IB) mortality, and survival for combined hepatocellular-cholangiocarcinoma (cHCC-CC) utilizing a population-based database to attract people’s attention to this disease. The Surveillance, Epidemiology, and End Results (SEER) database was utilized to investigate the incidence and IB mortality for cHCC-CC from 2000 to 2014. Trends in age-adjusted incidence and IB mortality were characterized by the Joinpoint Regression program. The Kaplan-Meier method and log-rank test were utilized to implement survival analyses. Cox regression was utilized to estimate independent predictors of mortality. The incidence of cHCC-CC was 0.26 per 1,000,000 individuals in 2000 and 0.59 per 1,000,000 individuals in 2014, with an annual percent change (APC) (i.e., the extent of increase in incidence) of 3.84% (95% confidence interval [CI] 1.7–6.1; P < 0.05). The IB mortality also displayed a sustained increase (APC was 4.59%, 95% CI 1.9–7.4; P < 0.05). Compared to patients not undergoing surgery, patients undergoing surgical treatment experienced a significant increase in median survival (3 vs. 28 months; P < 0.001). However, the median survival decreased in patients with tumor size > 5 cm (20 vs. 9 months; P < 0.001). Based on univariate Cox regression analysis, African-American race, distant stage, regionalized stage, tumor size ≥ 5 cm, and no surgery were risk factors for death. We identified an overall steady increase in the incidence of cHCC-CC, which indicates that primary prevention strategies for cHCC-CC have not improved much in recent years and that cHCC-CC needs to be taken seriously.

The ideal treatment for choledocholithiasis should be simple, readily available, reliable, minimally invasive and cost-effective for patients. We performed this study to compare the benefits and drawbacks of different laparoscopic approaches (transcystic and choledochotomy) for removal of common bile duct stones. A systematic search was implemented for relevant literature using Cochrane, PubMed, Ovid Medline, EMBASE and Wanfang databases. Both the fixed-effects and random-effects models were used to calculate the odds ratio (OR) or the mean difference (MD) with 95% confidence interval (CI) for this study. The meta-analysis included 18 trials involving 2,782 patients. There were no statistically significant differences between laparoscopic choledochotomy for common bile duct exploration (LCCBDE) (n = 1,222) and laparoscopic transcystic common bile duct exploration (LTCBDE) (n = 1,560) regarding stone clearance (OR 0.73, 95% CI 0.50–1.07; P = 0.11), conversion to other procedures (OR 0.62, 95% CI 0.21–1.79; P = 0.38), total morbidity (OR 1.65, 95% CI 0.92–2.96; P = 0.09), operative time (MD 12.34, 95% CI −0.10–24.78; P = 0.05), and blood loss (MD 1.95, 95% CI −9.56–13.46; P = 0.74). However, the LTCBDE group showed significantly better results for biliary morbidity (OR 4.25, 95% CI 2.30–7.85; P<0.001), hospital stay (MD 2.52, 95% CI 1.29–3.75; P<0.001), and hospital expenses (MD 0.30, 95% CI 0.23–0.37; P<0.001) than the LCCBDE group. LTCBDE is safer than LCCBDE, and is the ideal treatment for common bile duct stones.

Circulating tumor cells (CTCs) are considered potential biomarkers for the detection of hepatocellular carcinoma (HCC). Many studies have attempted to explore this role, but the results are variable. We conducted the first comprehensive meta-analysis to evaluate the diagnostic value of CTC assay for HCC patients. Additional prognostic value was also assessed. All articles included in our study were assessed using QUADAS guidelines after a literature search. Using bivariate generalized linear mixed model and random-effects model, effect measures such as pooled sensitivity/specificity, positive likelihood ratios/negative likelihood ratios (NLRs), diagnostic odds ratios, hazard ratios (HRs), risk ratios, and corresponding 95% confidence intervals (95% CIs) were calculated. We used receiver operating characteristic curves and area under the curve (AUC) to summarize overall test performance. Heterogeneity, publication bias, subgroup, and sensitivity analyses were also performed. A total of 2256 subjects including 998 HCC patients in 20 studies were recruited in this meta-analysis. Although the overall diagnostic accuracy of the CTC assay was high (AUC 0.93, 95% CI: [0.90–0.95]), there was a high probability of error rate (NLR 0.33, 95% CI: [0.23, 0.48]). The results were more robust when nonmagnetic-activated isolation was used, compared with magnetic-activated isolation subgroup (NLR: 0.18 vs. 0.41; z = 2.118, P = .034). CTCs positivity was significantly associated with relapse-free survival (HR 2.417, 95% CI: [1.421–3.250]; P < .001), overall survival (HR 3.59, 95% CI: [1.984–6.495]; P < .001), and some clinical characteristics. CTC assay is not recommended as an independent HCC diagnostic tool, but is associated with poor clinicopathologic characteristics of HCC patients and could indicate poor prognosis.