To investigate the relationship between Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), we determined gene expression profiles of discrete pathological stages of esophageal neoplasia using a sequence-verified human cDNA microarray. Fifty one RNAs, comprising 24 normal esophagi (NE), 18 BEs, and nine EACs were hybridized to cDNA microarrays. Five statistical analyses were used for the data analysis. Genes showing significantly different expression levels among the three sample groups were identified. Genes were grouped into functional categories based on the Gene Ontology Consortium. Surprisingly, the expression pattern of BE was significantly more similar to EAC than to NE, notwithstanding the known histopathologic differences between BE and EAC. The pattern of NE was clearly distinct from that of EAC. Thirty-six genes were the most differentially modulated, according to these microarray data, in BE-associated neoplastic progression. Twelve genes were significantly differentially expressed in cancer-associated BE's plus EAC (as a single combined tissue group) vs noncancer-associated BE's. These genes represent potential biomarkers to diagnose EAC at its early stages. Our results demonstrate that molecular events at the transcriptional level in BE are remarkably similar to BE's-associated adenocarcinoma of the esophagus. This finding alarmingly implies that BE is biologically closer to cancer than to normal esophagus, and that the cancer risk of BE is perhaps higher than we had imagined. These findings suggest that changes modulated at the molecular biologic level supervene earlier than histologic changes, and that BE is an early intermediate stage in the process of EAC.

Purpose: Portal vein tumor thrombus (PVTT) is a major complication of hepatocellular carcinoma (HCC) and is associated with poor survival. Long noncoding RNAs (lncRNA) contribute to HCC metastasis, but whether and how lncRNAs affect PVTT development remains unclear. In the present study, a novel highly expressed lncRNA (ICAM-1-related, ICR) was identified in ICAM-1 þ cancer stem cells (CSC) in HCC. This lncRNA regulated CSC properties and contributed to PVTT development.Experimental Design: We used microarray and bioinformatics analyses to identify differentially expressed lncRNAs. Realtime PCR and Western blotting were used to assess gene expression in cell lines and tumors. Sphere formation assays were performed to investigate stem cell properties of tumor cells in vitro. Retrospective and prospective studies were used to investigate the relationship between ICR expression and clinical outcomes. Conclusions: Our study demonstrates that ICR specifically regulates CSC properties of ICAM-1 þ HCC cells and that ICR contributes to PVTT development. Therefore, ICR may be a promising target for HCC therapy.

BackgroundNo consensus treatment has been reached for hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). Hepatic resection (HR) and transarterial chemoembolization (TACE) have been recommended as effective options, but which is better remains unclear. This meta-analysis is to compare the effectiveness of HR and TACE for HCC with PVTT patients.MethodsThe PubMed, EMBASE, Cochrane Library, VIP, Wan Fang, and Sino Med databases were systematically searched for comparing HR and TACE treating PVTT.ResultsTwelve retrospective studies with 3129 patients were included. A meta-analysis of 11 studies suggested that the 1-, 2-, 3-, and 5-year overall survival (OS) rates (OR = 0.48, 95% CI = 0.41–0.57, I2 = 37%, P < 0.00001; OR = 0.21, 95% CI = 0.12–0.38, I2 = 43%, P < 0.00001; OR = 0.35, 95% CI = 0.28–0.44, I2 = 53%, P < 0.00001; OR = 0.28, 95% CI = 0.14–0.54, I2 = 72%, P = 0.0001, respectively) favored HR over TACE. In a subgroup analysis, HR had better 1-, 2-,3, 5-year OS for type I PVTT (OR = 0.33, 95% CI = 0.17–0.64, I2 = 20%, P = 0.001; OR = 0.32, 95% CI = 0.16–0.63, I2 = 0%, P = 0.001; OR = 0.18, 95% CI = 0.09–0.36, I2 = 0%, P < 0.00001; OR = 0.07, 95% CI = 0.01–0.32, I2 = 0%, P = 0.0006, respectively) and better 1-, 3-, and 5-year OS for type II PVTT (OR = 0.37, 95% CI = 0.20–0.70, I2 = 59%, P = 0.002; OR = 0.22, 95% CI = 0.13–0.39, I2 = 0%, P < 0.00001; OR = 0.16; 95% CI = 0.03–0.91; I2 = 51%, P = 0.04, respectively). There was no difference in 1-, 3-, or 5-year OS between HR and TACE for type III PVTT (OR = 0.86, 95% CI = 0.61–1.21, I2 = 0%, P = 0.39; OR = 0.83, 95% CI = 0.42–1.64, I2 = 0%, P = 0.59; OR = 0.59, 95% CI = 0.06–-6.04, I2 = 65%, P = 0.66, respectively).ConclusionsHR may lead to longer OS for some selected HCC patients with PVTT than TACE, especially for type I or II PVTT, with less difference being observed for type III or IV PVTT.

Polarity defects are frequently involved in liver diseases, such as chronic hepatitis and hepatocellular carcinoma (HCC). It was reported that vacuolar protein sorting 33B (Vps33b) plays critical roles in the maintenance of hepatocyte polarity; however, the functional roles and mechanisms of Vps33b in HCC occurrence and progression remain unknown. First of all, we showed that Vps33b is down-regulated in human and mouse liver cancer samples, and the low expression levels of Vps33b correlate with the poor prognosis of many HCC patients. Liver-specific Vps33b deficiency induces liver damage, progressive hepatitis, fibrosis, and HCC in male mice, indicating that Vps33b is a crucial contributory factor to hepatocarcinogenesis. Vps33b deficiency-caused liver damage was primarily due to the disorders of structural and functional hepatocyte polarity, which were reflected by the decreased protein levels of E-cadherin because of inaccurate location to lysosomes and polarity defects at both apical and lateral plasma membrane proteins. The results of a mechanism study revealed that Vps33b interacts with VPS33B-interacting protein, which is involved in polarity and apical protein restriction; vesicle-trafficking protein Sec22b; and Flotillin-1 in hepatocytes and is in charge of the normal distribution of polarity-determined proteins. Expression levels of Vps33b negatively correlated with the degree of inflammatory cell infiltration in livers from diethylnitrosamine-induced or transgenic HCC mouse models, and the inflammatory stimuli suppressed the expression of Vps33b in vitro. Conclusion: Down-regulation of Vps33b expression is a critical step for inflammation-driven HCC, and Vps33b serves as an important tumor suppressor in hepatocarcinogenesis.

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