Objective To evaluate the effect of p53 on pyroptosis and its inhibitory role on tumor growth in non-small-cell lung cancer (NSCLC). Methods The correlation of p53 and pyroptosis was determined in tumor tissues of NSCLC patients. The pyroptotic level was detected in A549 cells to clarify the effect of p53 on pyroptosis. p53 overexpression A549 tumor-bearing mice were used to clarify the therapeutic target of p53 in NSCLC treatment. Results p53 expression level was positively related to pyroptosis in NSCLC tissues. In in vitro assays, p53 directly regulated pyroptosis in A549 cells. p53-specific knockdown blocked lipopolysaccharide- (LPS-) induced pyroptosis. In in vivo assays, p53 overexpression in A549 markedly decreased tumor growth and death rate by increasing the pyroptotic level. Conclusions Upregulation of p53 prompts pyroptosis to produce anti-NSCLC effects suggesting the potential of p53 on suppressing tumor growth in NSCLC patients.

This retrospective study was designed to investigate the correlation between a novel immunosubtyping method for hepatocellular carcinoma (HCC) and biological behavior of tumor cells. A series of 346 patients, who received hepatectomy at two surgical centers from January 2007 to October 2010, were enrolled in this study. The expressions of cytokeratin 19 (CK19), glypican 3 (GPC3), and CD34 were detected by immunohistochemical staining. The clinical stage was assessed using the sixth edition tumor–node–metastasis (TNM) system (UICC/AJCC, 2010).Vascular invasion comprised both microscopic and macroscopic invasion. The tumor size, lymph node involvement, and metastasis were determined by pathological as well as imaging studies. Recurrence was defined as the appearance of new lesions with radiological features typical of HCC, seen by at least two imaging methods. Survival curves for the patients were plotted using the Kaplan–Meier method, and differences between the curves were assessed using the log-rank test. Significant differences in morphology, histological grading, and TNM staging were observed between groups. Based on the immunohistochemical staining, the enrolled cases were divided into CK19+/GPC3+, CK19−/GPC3+ and CK19−/GPC3− three subtypes. CK19+/GPC3+ HCC has the highest risk of multifocality, microvascular invasion, regional lymph node involvement, and distant metastasis, followed by CK19−/GPC3+ HCC, then CK19−/GPC3−HCC. CK19+/GPC3+ HCC has the shortest recurrence time compared to other immunophenotype HCCs. CK19 and GPC3 expression profiling is an independent prognostic indicator in patients with HCC, and a larger sample size is needed to further investigate the effect of this immunosubtyping model in stratifying the outcome of HCC patients.

Ten to twenty percent of the hepatocellular carcinoma (HCC) patients fulfilling the Milan criteria (MC) recurred within three years after orthotopic liver transplantation (OLT). We therefore utilize a training cohort to develop an improved prognostic model for predicting the recurrence in these patients. By univariate and multivariate analysis, AFP level [cut-off value: 321 ng/mL, area under the curve (AUC) = 0.724, 95% confidence interval (CI) = 0.604–0.843, P < 0.001] and cytokeratin-19 (CK19) and glypican-3 (GPC3) expression pattern from nine putative prognostic factors were entered in risk factor scoring model to conjecture the tumor recurrence. In the training cohort, the AUC value of the model was 0.767 (95% CI = 0.645–0.890, P < 0.001), which was the highest among all the elements. The model’s performance was then assessed using a validation cohort. In the validation cohort, the AUC value of the model was 0.843 (95% CI = 0.720−0.966, P < 0.001) which was higher than any other elements. The results indicated that model had high performance with good discrimination ability and significantly improved the predictive capacity for the recurrence of HCC patients within MC after OLT.

Approximately 50% hepatocellular carcinoma patients meeting the Milan criteria utilized to develop an improved prognostic model for predicting the recurrence in these patients. Using univariate and multivariate analysis, cytokeratin-19 and glypican-3 expression patterns, tumor number and histological grading from eight putative prognostic factors comprised the risk factor scoring model to predict the tumor recurrence. In the training cohort, the area under roc curve (AUC) value of the model was 0.715 [95% confidence interval (CI) = 0.645−0.786, P<0.001], which was the highest among all the parameters. The performance of the model was assessed using an independent validation cohort, wherein the AUC value was 0.760 (95% CI=0.647−0.874, P<0.001), which was higher than the other factors. The results indicated that model had high performance with adequate discrimination ability. Moreover, it significantly improved the predictive capacity for the recurrence in patients with hepatocellular carcinoma within the Milan criteria after radical resection.

Hepatocellular carcinomas(HCC) consisted of heterogeneous subtypes with different recurrence probabilities after liver transplantation(LT). Our study aimed to develop an improved model for predicting the recurrence of solitary HCC after LT. In this retrospective study, 151 solitary HCC patients who received orthotopic LT over a period of 10 consecutive years were included. All recipients received graft from deceased donors. The first eligible 50 patients were used as validation cohort and others were utilized to construct the model. A two-tailed P < 0.05 was considered to indicate statistical significance for all analysis. Based on the maximisation of the Youden’s index, the optimal cutoff values for alpha-fetoprotein(AFP) and tumor diameter were 261.6 ng/mL and 3.6 cm, respectively. Vascular involvement includes gross and microscopic vascular invasion. Variables potentially affecting recurrence-free survival(RFS) were examined using univariate and multivariate Cox regression analysis. Univariate and multivariate analysis revealed that AFP, tumor diameter, vascular invasion and cytokeratin-19/glypican-3 sub-typing were independent prognostic factors for RFS, thus comprised the risk scoring model. The AUC values of the model in the cohorts were significantly higher than that of the Milan, UCSF, Fudan and Hangzhou criteria. These findings suggest the model has high performance in predicting early recurrence of solitary HCC patients after LT.

The primary epithelial tumors of the liver (PETL) are composed of a series of heterogeneous tumors. Although the classification of PETLs has been updated several times by the World Health Organization, the cellular origins of some tumors in this family remain to be precisely depicted. In addition, certain tumors in different categories have similar histology, molecular phenotypes and biological characteristics, suggesting that they may have the same cellular origin. In this work, a narrative review method was adopted to review the relevant papers. By comparing the expression profiles of biomarkers of liver epithelium at different lineages and stages of differentiation, the cells-of-origin of some major members of the PETL family were reassessed. We propose that 1) hepatic adenomas, hepatocellular carcinomas (HCCs) and pure fetal hepatoblastomas (HBs) share the same spectrum in their cellular origin including the hepatocytic-committed progenitors (HCP) and their differentiated descendants. 2) Bile duct adenomas, peribiliary cysts and intrahepatic cholangiocellular carcinomas (ICCs) can share the same spectrum in their cellular origin including the cholangiocytic-committed progenitors (CCP) and their differentiated descendants. 3) The cells-of-origin of embryonal HBs include liver stem cells (LSCs), hepatoblasts, and transitional cells between them. Embryonal HB with small cell element, small cell undifferentiated HB and small cell neuroendocrine carcinoma of the liver can have the same or similar cellsof-origin from LSC. Embryonal HB lacking the small cell component of the LSC phenotype and presenting both hepatocytic and bile duct/ductule components may originate from actual hepatoblasts/hepatic progenitor cells (HPCs) as the combined HCC-ICC does. 4) Teratoid hepatoblastoma and mixed epithelial/mesenchymal HBs can be derived from the LSCs or even less committed extrahepatic pluripotent stem cell. 5) Many members of the PETLs family, including those derived from LSCs, hepatoblasts/HPCs, early HCPs and CCPs, have neuroendocrine potentiality. Except for those primary hepatic neuroendocrine tumor (PHNET) exhibit hepatocytic and/or cholangiocytic phenotypes, other PHNETs subtype may be derived from the descendants of LSC that differentiate towards the upper digestive tract, pancreas or other lineages.

PurposeThis study aimed to explore the circular RNA (circRNA/circ) profile engaged in non-small cell lung cancer (NSCLC) development and metastasis and to investigate potentially key carcinogenic circRNAs related to NSCLC.MethodsCircRNA profiles between 10 NSCLC tissues and 10 adjacent tissues and between five NSCLC tissues with lymph node metastasis (LNM) and five NSCLC tissues without LNM were detected by Arraystar Human circRNA Array followed by bioinformatics. Circ_0008594 knockdown, circ_0004293 overexpression, and circ_0003832 overexpression plasmids were transfected into H23 and H460 cells to sort potential oncogenic circRNA. Then circ_0008594 overexpression and knockdown plasmids were transfected, followed by that circ_0008594 knockdown plus miR-760 knockdown plasmids were transfected into these cells. Cell proliferation, apoptosis, invasion, stemness, and pathways were detected. In addition, xenograft mice models were constructed via injecting H23 cells with circ_0008594 overexpression or knockdown to validate the findings.ResultsA total of 455 dysregulated circRNAs in NSCLC tissues versus adjacent tissues and 353 dysregulated circRNAs in NSCLC tissues with LNM versus those without LNM were discovered. Via cross-analysis, 19 accordant circRNAs were uncovered, among which three candidate circRNAs (circ_0008594, circ_0004293, circ_0003832) were chosen for functional experiments, during which it was observed that circ_0008549 affected H23 and H460 cell proliferation and apoptosis more obviously than circ_0004293 and circ_0003832. Subsequent experiments showed that circ_0008594 promoted H23 and H460 cell proliferation and invasion but affected stemness less and negatively regulated miR-760 via direct binding. Furthermore, miR-760 attenuated the effect of circ_0008549 on regulating H23 and H460 cell functions and the PI3K/AKT and MEK/ERK pathways. In vivo experiments further confirmed that circ_0008549 increased tumor volume, epithelial-mesenchymal transition, and the PI3K/AKT and MEK/ERK pathways while reducing tumor apoptosis and miR-760 NSCLC xenograft models.ConclusionOur study identifies several valuable circRNAs related to NSCLC development and LNM. Furthermore, as a key functional circRNA, circ_0008594 was observed to promote NSCLC progression by regulating the miR-760-mediated PI3K/AKT and MEK/ERK pathways.

BACKGROUND Pathological manifestations of hepatic tumours are often associated with prognosis. Although surgical specimens (SS) can provide more information, currently, pre-treatment needle core biopsy (NCB) is increasingly showing important value in understanding the nature of liver tumors and even in diagnosis and treatment decisions. However, the concordance of the clinicopathological characteristics and immunohistochemical (IHC) staining between NCB and SS from patients with hepatic tumours were less concerned. AIM To introduce a more accurate method for interpreting the IHC staining results in order to improve the diagnostic value of hepatic malignancy in NCB samples. METHOD A total of 208 patients who underwent both preoperative NCB and surgical resection for hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) between 2008 and 2015 were enrolled in this study. The expression of CK19, GPC3, and HepPar1 were detected by IHC staining. Clinicopathological, NCB, and surgical data were collected and analysed using χ 2 and kappa statistics. RESULTS Morphologically, the presence of compact tumour nests or a cord-like structure in NCB was considered the primary cause of misdiagnosis of HCC from ICC. The kappa statistic showed a moderate agreement in histomorphology (k = 0.504) and histological grade (k = 0.488) between NCB and SS of the tumours. A 4-tier (+++, ++, +, and -) scoring scheme that emphasized the focal neoplastic cell immunoreactivity of tumour cells revealed perfect concordance of CK19, GPC3 and HepPar1 between NCB and SS (k = 0.717; k = 0.768; k = 0.633). Furthermore, with the aid of a binary classification derived from the 4-tier score, a high concordance was achieved in interpreting the IHC staining of the three markers between NCB and final SS (k = 0.931; k = 0.907; k = 0.803), increasing the accuracy of NCB diagnosis C (k = 0.987; area under the curve = 0.997, 95%CI: 0.990-1.000; P < 0.001). CONCLUSION These findings imply that reasonable interpretation of IHC results in NCB is vital for improving the accuracy of tumour diagnosis. The simplified binary classification provides an easy and applicable approach.