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.

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.

Our aim was to determine the epidemiology and recent changes in the trends of non-functional pancreatic neuroendocrine tumours (NF-pNETs) at the population level. In addition, we explored the risk factors that are associated with survival duration. Cases were identified form the Surveillance, Epidemiology, and End Results (SEER) Programme database from 2000 to 2014. Data on incidence and incidence-based (IB) mortality for NF-pNET were obtained from this database. Secular trends in age-adjusted incidence and IB mortality were determined by using the Joinpoint Regression program. Data analyses were performed using chi-square tests, Kaplan-Meier curves and Cox proportional hazards regression. Overall, 4766 patients diagnosed with NF-pNET with a median age of 59 years were identified through our descriptive criteria. Caucasian patients accounted for the majority of the study population, and the proportion of patients with distant disease significantly decreased during our study period. Overall, there was an increase in incidence and IB mortality for NF-pNET; however, the rate of increase decreased during the recent years. In addition, the incidence trends of NF-pNET located in the pancreatic head significantly increased, and rates fo increase in IB mortality for NF-pNET in the pancreatic tail decreased in recent years. Additionally, the 1-, 5-, and 10-year survival rates were 79.0, 51.8, 38.1%, respectively. Furthermore, patient age, tumour grade, stage at diagnosis, tumour size, tumour site and resection were associated with mortality. Despite increases in incidence and IB mortality, the rate of change in IB mortality for NF-pNET has decreased in recent years. Survival duration displayed a secular increase during the overall period, and the prognosis and survival duration of patients were closely related to the time of diagnosis, age of the patients and size and location of the tumour. Appropriate treatment adjustments based on tumour stage may thus facilitate improvements in patient outcomes.

Purpose: Numerous studies have shown that the expression of microRNA-181c (miR-181c) is inhibited in various cancers, which suggests that it has a cancer suppressive effect. In the current study, we evaluated the regulation and characteristics of miR-181c in human hepatocellular carcinoma (HCC). Materials and methods: Samples of tumor tissues and adjacent non-tumor tissues were collected from 52 patients with HCC, and expression levels of miR-181c in these samples were investigated via quantitative real-time polymerase chain reaction. HCC cell migration and invasion were investigated via wound healing assays and transwell assays. HCC cell apoptosis rates were assessed via flow cytometry, and HCC proliferation was assessed via 5-ethynyl-20-deoxyuridine assays. In vivo tumors were initiated by subcutaneously inoculating HCC cells into nude mice. And various biomarkers were investigated via western blotting. Results: In microarray datasets and tumor tissues, significant downregulation of miR-181c was apparent compared with non-tumorous adjacent tissues. Expression of miR-181c in HCC cells was also significantly lower than it was in normal human liver cells. miR-181c regulated the migration, invasion, apoptosis, and proliferation of HCC cell lines in vitro, and tumor development in vivo. Observations also suggest that miR-181c regulates NCAPG in HCC cells, and its expression affects cellular invasion, migration, proliferation, and apoptosis. There was a negative correlation between miR-181c expression and NCAPG in HCC tissue samples. Conclusion: miR-181c exhibits tumor-suppression via the regulation of NCAPG levels.

Exosome DNA (exoDNA) can be used for liquid biopsy. This study was the first to use droplet digital PCR (ddPCR) to detect tumor-specific mutations in exoDNA and to evaluate the prognosis of hepatocellular carcinoma (HCC) patients. 60 HCC patients were enrolled in the study. We used ddPCR to detect c.747 G > T mutation in TP53 gene. We analyzed the correlation between detectable mutation in exoDNA and clinicopathologic characteristics using Multivariate logistics regression analysis. We performed Cox regression to assess the correlation between mutation frequency (mutant droplets/total droplets, MD/TD) and prognostic. We found that 48 of 60 patients had c.747 G > T mutation in TP53 gene in exoDNA (80.0%). We found that detectable mutation in exoDNA and age were associated with microvascular invasion (MVI) (P < .01). The ROC curve analysis revealed that the best cutoff value of mutation frequency to predict MVI was 67% (sensitivity 48.15%, specificity 93.94%,), the corresponding AUC was 0.761 (95%CI, 0.640–0.866; P < .01). Furthermore, we found that patients suffered high-frequency mutation (>67%) had shorted median recurrence-free survival (RFS) with 63 days (range, 53–202 days), compared with 368 days (range, 51–576 days) for patients with low-frequency mutation (<67%) (HR:4.61; 95% CI, 1.70–12.48; P = 0 .003). We also found that high-frequency mutation was associated with poor prognosis though patients had better pathological characteristics, such as AFP (<400 ng/mL), Liver cirrhosis (Negative), Tumor thrombus (Negative), Tumor numbers (Single) and Post-operation TACE (Executed). We provided evidence that the mutations in exoDNA might be used to predict patients with poor RFS. Abbreviations: TP53: Tumor protein p53; ExoDNA: Exosomal DNA; HCC: Hepatocellular carcinoma; ddPCR: Droplet digital Polymerase Chain Reaction (PCR); MD/TD: The ratio of mutant droplets/total droplets; AFP: Alpha-fetoprotein; MVI: Microvascular invasion; RFS: Recurrence-free survival.

Background: The rise in incidence and mortality of gastrointestinal mixed adenoneuroendocrine carcinoma (MANEC) has not been well focused. The aim of our study was to examine epidemiological trends in incidence and incidence-based (IB) mortality of gastrointestinal MANEC at a population level. Methods: The incidence and IB mortality of gastrointestinal MANEC as well as data on affected patients from 2000 to 2016 were obtained from the Surveillance, Epidemiology, and End Results database. Trends in incidence and IB mortality were assessed using Joinpoint regression. The Kaplan–Meier method and log-rank test were used for survival analysis. Cox proportional hazards regression was used to identify independent predictors of mortality. Results: 581 patients diagnosed with gastrointestinal MANEC were enrolled. Gastrointestinal MANEC incidence was 0.23 cases per 1,000,000 individuals in 2000 and 1.16 cases per 1,000,000 individuals in 2016, with an annual percent change (APC) of 8.0% (95% CI 5.7–10.3%, P < 0.05). IB mortality also showed a sustained increase (APC 12.9%, 95% CI 9.0–16.8%, P < 0.05). In Cox regression analysis, age at diagnosis, tumor grade and stage, lymph node metastasis, surgery, and tumor size were independently associated with mortality. Median survival was 75 months (95% CI 60–128 months). Median survival of appendiceal MANEC was significantly longer than that of cecal MANEC (115 vs. 31 months; P < 0.001). Conclusions: We found a sustained and rapid increase both in incidence and IB mortality of gastrointestinal MANEC, manifesting that there has been no significant improvement in patient outcomes, nor progress in prevention and treatment. Additional resources should be devoted to gastrointestinal MANEC research.