The facilitating effects of KRT80 on chemoresistance, lipogenesis, and invasion of esophageal cancer.

Keratin 80 (KRT80) is a filament protein that makes up one of the major structural fibers of epithelial cells, and involved in cell differentiation and epithelial barrier integrity. Here, KRT80 mRNA expression was found to be higher in esophageal cancer than normal epithelium by RT-PCR and bioinformatics analysis (p < .05), opposite to KRT80 methylation (p < .05). There was a negative relationship between promoter methylation and expression level of KRT80 gene in esophageal cancer (p < .05). KRT80 mRNA expression was positively correlated with the differentiation, infiltration of immune cells, and poor prognosis of esophageal cancer (p < .05). KRT80 mRNA expression was positively linked to no infiltration of immune cells, the short survival time of esophageal cancers (p < .05). The differential genes of KRT80 mRNA were involved in fat digestion and metabolism, peptidase inhibitor, and intermediate filament, desosome, keratinocyte differentiation, epidermis development, keratinization, ECM regulator, complement cascade, metabolism of vitamins and co-factor (p < .05). KRT-80-related genes were classified into endocytosis, cell adhesion molecule binding, cadherin binding, cell-cell junction, cell leading edge, epidermal cell differentiation and development, T cell differentiation and receptor complex, plasma membrane receptor complex, external side of plasma membrane, metabolism of amino acids and catabolism of small molecules, and so forth (p < .05). KRT80 knockdown suppressed anti-apoptosis, anti-pyroptosis, migration, invasion, chemoresistance, and lipogenesis in esophageal cancer cells (p < .05), while ACC1 and ACLY overexpression reversed the inhibitory effects of KRT80 on lipogenesis and chemoresistance. These findings indicated that up-regulated expression of KRT80 might be involved in esophageal carcinogenesis and subsequent progression, aggravate aggressive phenotypes, and induced chemoresistance by lipid droplet assembly and ACC1- and ACLY-mediated lipogenesis.

The promoting effects of GPR176 expression on proliferation, chemoresistance, lipogenesis and invasion of oesophageal cancer.

PURPOSE: As a member of the G-protein-coupled receptor 1 family, the G-protein-coupled receptor 176 (GPR176) gene encodes a glycosylated protein made up of 515 amino acids. The current study was performed to evaluate the impact of GPR176 on the clinicopathology and prognosis of oesophageal cancer, as well as uncover its molecular mechanisms. METHODS: Bioinformatics and clinical tissue samples were used to detect the expression and clinicopathological significance of GPR176 in oesophageal cancer. The expression, proliferation, migration and invasion, apoptosis and lipid droplet formation of GPR176 gene in oesophageal cancer were performed as phenotypic readouts. RESULTS: Here, RT-PCR and bioinformatic analyses revealed that GPR176 mRNA expression was significantly higher in oesophageal cancer than in normal mucosa (p < 0.05). GPR176 mRNA expression was associated with low weight and BMI, low T stage, low N and clinicopathological stage, low histological grade and favourable clinical outcome of oesophageal cancer (p < 0.05). The differential genes of GPR176 mRNA were involved in protein digestion and absorption, extracellular matrix constituent, endoplasmic reticulum lumen, among others (p < 0.05). GPR176-related genes were classified as being involved in oxidoreductase activity, actin and myosin complexes, lipid localisation and transport, among others (p < 0.05). GPR176 knockdown suppressed proliferation, anti-apoptotic and anti-pyroptotic properties, migration, invasion, chemoresistance and lipid droplet formation in oesophageal cancer cells (p < 0.05), while ACC1 and ACLY overexpression reversed the inhibitory effects of GPR176 silencing on lipid droplet formation and chemoresistance. CONCLUSION: These findings indicated that upregulated expression of GPR176 might be involved in oesophageal carcinogenesis and subsequent progression, aggressiveness, and induced chemoresistance by ACC1- and ACLY-mediated lipogenesis and lipid droplet assembly.

Clinical Value of Tumor Marker Index Based on Preoperative CYFRA 21-1 and SCC-Ag in the Evaluation of Prognosis and Treatment Effectiveness in Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: This study aimed to investigate the prognostic value of tumor marker index (TMI) based on preoperative cytokeratin 19 fragment (CYFRA 21-1) and squamous cell carcinoma antigen (SCC-Ag) and the relationship between preoperative TMI and treatment effectiveness of postoperative adjuvant chemotherapy for patients with esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Between January 2009 and December 2014, a total of 267 patients with ESCC who underwent radical resection were retrospectively enrolled. The TMI was defined as the geometric mean of normalized CYFRA 21-1 and SCC-Ag levels. The clinical and prognostic values of TMI were determined using univariate and multivariate survival analyses. RESULTS: Preoperative TMI level was associated with age, tumor size, pT stage, pN stage, and CYFRA 21-1, SCC-Ag, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) levels. The 5-year overall survival rate of patients with high TMI was significantly lower than that of patients with low TMI (P < 0.001). Univariate and multivariate analyses revealed that TMI (P = 0.031) was an independent prognostic factor. Patients with ESCC with high TMI level who underwent surgery combined with postoperative chemotherapy had a significantly better prognosis than those who underwent surgery alone (P = 0.015). However, no significant difference was observed in patients with low TMI level (P = 0.682). CONCLUSION: TMI as a prognostic indicator of ESCC is superior to CYFRA 21-1 and SCC-Ag. The TMI might be useful in predicting the therapeutic effectiveness of postoperative chemotherapy and selecting patients who may benefit from postoperative chemotherapy.

Cav-1 promote lung cancer cell proliferation and invasion through lncRNA HOTAIR.

OBJECTIVES: Lung cancer is one of the most common malignant tumors worldwide, and its morbidity and mortality rates continue to rise. The role of lncRNAs in lung cancer has become an emerging area of research. MATERIALS AND METHODS: The expression of CAV-1 and HOTAIR was determined in lung cancer tissues and cell lines by western blot and RT-qPCR. Cell proliferation, migration and invasion were analysed in lung cell following knockdown or overexpression of CAV-1 or HOTAIR by transfection with small interfering RNA (siRNA) or plasmid. RESULTS: The expression of CAV-1 and HOTAIR in lung cancer tissues and cell lines was higher than in normal lung tissue or normal lung cell lines. We discovered that CAV-1 could regulate cell proliferation, migration and invasion. At the same time, CAV-1 could regulate the expression of HOTAIR. In addition, knockdown of the expression of HOAIR partially reverses the promotion of cell viability and invasion induced by CAV-1. CONCLUSIONS: Our results indicated that CAV-1 coordinate the lung cancer through HOTAIR. And HOTAIR may become a novel target for lung cancer therapy.

Combination of platelet count and lymphocyte to monocyte ratio is a prognostic factor in patients undergoing surgery for non-small cell lung cancer.

The aim of this study was to investigate the usefulness of a novel inflammation-based prognostic system, called COP-LMR (combination of platelet count and lymphocyte to monocyte ratio), for predicting postoperative survival of patients with non-small cell lung cancer (NSCLC). COP-LMR was calculated on the basis of the obtained data. Patients with both an elevated platelet count (PLT) (>30 × 104mm-3) and a low LMR (<3.6) were assigned a score of 2, and patients with one or none of the parameters were assigned a score of 1 or 0, respectively. A total of 1120 patients who underwent complete resection were enrolled in this study. Multivariate analysis revealed that COP-LMR is an independent prognostic factor for disease-free survival (DFS) (P<0.001) and overall survival (OS) (P<0.001). Kaplan-Meier analysis and the log-rank test revealed that COP-LMR stratified the patients into 3 independent groups (P<0.001). In conclusion, COP-LMR is a potential prognostic biomarker in patients undergoing surgery for NSCLC.

Prognostic significance of subclassification of stage IIB lung cancer: a retrospective study of 226 patients.

We investigated the prognostic significance of subclassification of stage IIB lung cancer according to the eighth tumor-node-metastasis (TNM) classification. To this purpose, the prognostic outcomes of 226 stage IIB lung cancer patients who underwent surgery without adjuvant therapies between 2001 and 2010 were evaluated retrospectively based on the eighth TNM classification. Of the 226 patients, 23, 30, 118 and 55 had pT1b, pT1c, pT2a, and pT2b stage cancers, respectively. Their 5-year survival rates were 67%, 33%, 21%, and 27%, respectively. There was no significant difference in the 5-year survival between T1b and T1c, between T1c and T2a, and between T2a and T2b (p = 0.128, 0.105, and 0.403, respectively). There were significant differences in the 5-year survival between T1b and T2a, between T1b and T2b, and between T1c and T2b (p = 0.005, 0.002, and 0.042, respectively). The 5-year survival of patients with pleural invasion and vessel invasion was significantly worse than that of their counterparts (p = 0.009 and <0.001, respectively). Subclassification of stage IIB lung cancer is of prominent prognostic significance. It is recommended that the current stage be subclassified, in order to more accurately predict the prognosis of patients.

Curcumin Ameliorates Diabetic Nephropathy by Suppressing NLRP3 Inflammasome Signaling.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, partly because of the lack of effective treatments for DN. Curcumin has been shown to exert strong antifibrotic effects in DN, but the underlying mechanisms are not well characterized. In this study, we sought to determine the effects of curcumin on diabetic renal disease in db/db mice and characterize the underlying mechanism of action. We administered curcumin to db/db mice for 16 weeks. In comparison to mock-treated db/db mice, curcumin-treated mice showed diminished renal hypertrophy, reduced mesangial matrix expansion, and a lower level of albuminuria. Furthermore, the upregulated protein and mRNA expressions of collagen IV and fibronectin in the renal cortices of the db/db mice were inhibited by curcumin treatment. Additionally, curcumin treatment was associated with significant reductions in mature interleukin-1ß, cleaved caspase-1, and NLRP3 protein levels in the renal cortices of db/db mice as well as in HK-2 cells exposed to high glucose concentration. In summary, curcumin, a potent antifibrotic agent, is a promising treatment for DN, and its renoprotective effects appear to be mediated by the inhibition of NLRP3 inflammasome activity.

Clinical significance of GRHL3 expression in diffuse large B cell lymphoma.

In the present study, we assessed the GRHL3 expression in 967 patients with diffuse large B cell lymphomas to identify the potential prognostic value and the development of specific therapeutic strategies. All patients enrolled were from a previous study by Hao Zhang et al. (BMC Cancer 14:333, 2014). GRHL3 expression status was evaluated by immunohistochemical analysis. Survival analysis using the Kaplan-Meier method and multivariate analysis were conducted to adjust the effect of GRHL3 expression as a potential independent prognostic factor. In the enrolled 967 patients, GRHL3 expression was detected in 398 (41.16 %) patients under immunohistochemical analysis. The 5-year survival rate in patients with GRHL3 expression was significantly lower than that in those without GRHL3 expression (37.8 vs 52.8 %, P < 0.001). Multivariate analysis identified GRHL3 expression as an independent predictor of poor survival. The sensitivity and specificity of GRHL3 for the diagnosis of germinal center B cell (GCB)/non-GCB was 89.2 % (182/204) and 82.1 % (174/212), respectively. GRHL3 expression may be useful as a prognostic factor and for the diagnosis GCB/non-GCB of diffuse large B cell lymphoma.