USP18 promotes tumor metastasis in esophageal squamous cell carcinomas via deubiquitinating ZEB1.

The dysregulation of deubiquitinating enzymes (DUBs), which regulate the stability of most cellular proteins, have been implicated in many human diseases, including cancers. Ubiquitin-specific protease 18 (USP18), a member of the DUBs family, functions as a potential tumour promoter in various cancers. However, the biological function and clinical significance of USP18 in esophageal squamous cell carcinomas (ESCC) are still unclear. Here, we found that ESCC tumors had higher USP18 expression compared with that of normal esophageal epithelial tissues, and high USP18 level was significantly correlated with malignant phenotype and shorter survival in patients with ESCC. In functional experiments, USP18 knockdown significantly inhibited ESCC invasion and metastasis in vitro. Consistently, a xenograft assay showed that knockdown of USP18 in ESCC cell suppressed their dissemination to lung tissue in vivo. Furthermore, we showed that USP18 promoted ESCC cell metastasis by inducing ZEB1 mediated epithelial-mesenchymal transition (EMT). Importantly, our results demonstrated that the oncogenic effect of USP18 in ESCC is partially dependent on ZEB1 enhancement. Mechanistic investigations revealed that USP18 directly bound ZEB1 and decreased its ubiquitination to enhance the protein stability of ZEB1 in ESCC cells. Overall, our data highlighted an essential role of USP18 in ESCC metastasis, suggesting that it could be a potential diagnostic and therapeutic target for ESCC.

Associations of candidate gene polymorphisms with poor responsiveness to aspirin: a meta-analysis.

Recently, the roles of gene polymorphisms in poor responsiveness to aspirin were extensively investigated, with conflicting results. Therefore, we performed this meta-analysis to better assess the relationship between candidate genetic variants and poor responsiveness to aspirin. Eligible articles were searched in PubMed, Medline, Embase and CNKI. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to detect possible associations of gene polymorphisms with poor responsiveness to aspirin. Among 53 eligible articles, a total of 22 candidate gene polymorphisms were analyzed. A significant association with poor responsiveness to aspirin was observed for GP1BA rs2243093, PTGS1 rs1330344, PTGS2 rs689466 and TBXA2R rs1131882 polymorphisms in overall analyses. Further subgroup analyses demonstrated that ITGA2 rs1126643, PTGS1 rs1330344, PTGS2 rs20417, PTGS2 rs689466 and TBXA2R rs1131882 polymorphisms were significantly associated with poor responsiveness to aspirin in Asians, whereas only GP1BA rs2243093 polymorphism was significantly correlated with this phenomenon in Caucasians. In conclusion, our findings indicate that GP1BA rs2243093, ITGA2 rs1126643, PTGS1 rs1330344, PTGS2 rs20417, PTGS2 rs689466 and TBXA2R rs1131882 polymorphisms may serve as genetic biomarkers of poor responsiveness to aspirin in certain ethnic groups. This article is protected by copyright. All rights reserved.

Base water potential but not hydrotime predicts seedling emergence of Medicago sativa under water stress conditions.

We determined the hydrotime model parameters of 10 alfalfa seed lots by incubating seeds at various water potentials in the laboratory. Meanwhile, seedling emergence under drought and salinity conditions in a greenhouse pot experiment, and seedling establishment in the field were determined. Correlation analysis was utilized to detect the relationship between hydrotime model parameters and seedling emergence under water stress conditions. The germination percentage did not differ significantly among seed lots when seeds were incubated at -0.1 MPa, while it differed significantly among seed lots at water potentials of -0.3 and -0.6 MPa. Compared to control conditions, drought and salinity decreased seedling emergence to different extents, depending on seed lots. Seedling emergence in the field differed significantly among seed lots and ranged from 30% to 80%. Ψ b(50) showed a significant correlation with seedling emergence under various conditions and with seedling establishment in the field, while no correlation was observed between θ H, σ φb and seedling emergence and establishment. These results suggest that Ψ b(50) can be used to rank the vigor of alfalfa seed lots and thus predict seedling emergence and establishment under water stress conditions.

Identification and verification of a prognostic ferroptosis-related lncRNAs signature for patients with lung adenocarcinoma.

Lung cancer has been identified as one of the deadliest malignant tumors worldwide. Mounting evidence suggests that ferroptosis is a well-known non-apoptotic cell death process that participates in pathological mechanisms and is a new cancer treatment strategy. Aberrantly expressed long non-coding RNAs (lncRNAs) that drive lung cancer progression have attracted increasing attention. Herein, we explored the prognostic significance of ferroptosis-related lncRNAs in lung cancer patients. LUAD gene expression patterns and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA) database. Based on LASSO-Cox regression, A 14 ferroptosis-related differentially expressed lncRNAs (FRDELs) signature was constructed. Subsequently, a nomogram model for predicting the prognosis of LUAD patients was constructed based on clinicopathological data and the 14 - FRDELs signature. The signature was shown to be correlated with tumor mutational burden (TMB) and immune cell infiltration within the tumor microenvironment. Furthermore, Gene Set Enrichment Analysis (GSEA) confirmed that the signature was correlated with LUAD-related biological functions such as the P53 signaling pathway, DNA replication, and cell cycle. The roles and mechanisms of PACERR in the signature were explored by si-lncRNA-mediated knockdown and transfection-mediated overexpression via in vitro experiments in A549 and H1299 cells. PACERR was significantly upregulated in A549 and H1299 cells, and higher expression promoted LUAD cell proliferation, migration, and invasion via in vitro experiments, while knockdown of PACERR presented the opposite effects. In conclusion, our study provided information regarding ferroptosis-related lncRNA expression and established a prognostic nomogram based on 14 FRDELs to predict overall survival in LUAD accurately. Additionally, our results in vitro revealed that PACERR played an oncogenic role in LUAD proliferation and metastasis, which provides mechanistic insights into the roles of ferroptosis-related lncRNA in LUAD progression and that it may be a potential biomarker for LUAD treatment.

Prognostic roles of mRNA expression of notch receptors in non-small cell lung cancer.

Notch signalling is aberrantly activated in human non-small cell lung cancer (NSCLC). Nevertheless, the prognostic roles of mRNA expression of four Notch receptors in NSCLC patients remain elusive. In this report, we reported the prognostic roles of Notch receptors in a total of 1,926 NSCLC patients through "The Kaplan-Meier plotter" (KM plotter) database which is capable to assess the effect of 22,277 genes on survival of NSCLC patients. We found that mRNA high expression level of Notch1 was associated with better overall survival (OS) for all NSCLC patients, hazard ratio (HR) 0.78 (0.69-0.89), p=0.00019, better OS in adenocarcinoma (Ade) patients, HR 0.59 (0.46-0.75), p=1.5e-05, as well as in squamous cell carcinoma (SCC) patients, HR 0.78 (0.62-0.99), p=0.044. mRNA high expression levels of Notch2 and Notch3 were associated with worsen OS for all NSCLC patients, as well as in Ade, but not in SCC patients. mRNA high expression level of Notch4 was not found to be associated with to OS for all NSCLC patients. In addition, mRNA high expression levels of Notch2, Notch3, but Notch4 are significantly associated with the NSCLC patients who have different smoking status. Our results indicate that mRNA expression of Notch receptors may have distinct prognostic values in NSCLC patients. These results will benefit for developing tools to accurately predict the prognosis of NSCLC patients.

Case-matched analysis of combined thoracoscopic-laparoscopic versus open esophagectomy for esophageal squamous cell carcinoma.

The aim of this study is to evaluate surgical results and long-term survival of combined thoracoscopic-laparoscopic esophagectomy (TLE) performed for esophageal squamous cell carcinoma. Data of 59 patients with esophageal squamous cell carcinoma, undergoing TLE from January 2007 to January 2015, were compared to a control group of 59 patients who underwent open esophagectomy (OE) during the same period. The two groups were matched in terms of age, sex, American Society of Anesthesiology (ASA) score and clinical TNM stage. Laparoscopic approach resulted in longer operating time (P=0.003) and lower blood loss (P=0.000). There was no difference in perioperative morbidity and mortality rate; TLE approach was associated with a shorter hospital stay (P=0.000). After a mean follow up of 38 months, 5-year disease free survival and 5-year overall survival were 38% and 50% for TLE group, and 36% and 45% for OE group (P>0.05). TLE for esophageal squamous cell carcinoma is feasible and safe in selected patients and can result in good surgical results, with similar outcomes in terms of long-term outcomes.

[Video-assisted thoracoscopic radical resection of early-stage non-small cell lung cancer].

OBJECTIVE: To study the reliability and feasibility of video-assisted thoracoscopic surgery (VATS) for radical resection of early-stage non-small cell lung cancer (NSCLC). METHODS: Fifty-four patients with NSCLC treated between Jan. 2007 and Jun. 2010 at our institution were divided into VATS group (n=23) and video-assisted mini thoracotomy (VAMT) group (n=31). The operative time, intraoperative blood loss, number of dissected nodes, pleural effusion drainage, postoperative hospital stay, and visual analogue scales (VAS) were compared between the two groups. RESULTS: No deaths or serious complications occurred perioperatively in the two groups. The operative time, intraoperative blood loss, number of dissected lymph nodes or pleural effusion drainage were all comparable between the two groups, but compared with VAMT, VATS was associated with significantly shortened postoperative hospital stay (10.54±1.21 days vs 7.92±0.86 days, P<0.05) and lowered VAS scores (4.26±1.28 vs 2.37±0.25, P<0.05). CONCLUSION: VATS for pulmonary lobe resection with systematic node dissection is a feasible approach to the management of early-stage NSCLC.