ABSTRACT
BACKGROUND: The CAV family, especially CAV1 and CAV2, is significantly associated with tumor development. In this study, we aimed to explore the pathogenic and prognostic roles of CAV1 and CAV2 in head and neck squamous cell carcinoma (HNSCC) through bioinformatic analysis and verified in human tissue. METHODS: We analyzed expression profiles of CAV1 and CAV2 in HNSCC and in normal tissues via data from The Cancer Genome Altas. Prognostic significance was examined by Kaplan-Meier survival curve obtained from the Xena browser together with Cox regression analysis. Co-expressed genes were uploaded to GeneMANIA and applied to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, showing interaction networks. Signaling pathways of CAV1 and CAV2 in HNSCC were analyzed by Gene Set Enrichment Analysis to elucidate potential regulatory mechanisms. Gene-drug interaction network was explored via Comparative Toxicogenomics Database. Immunohistochemistry was performed to verify theoretical results. RESULTS: Compared with normal tissues, expression levels of CAV1 and CAV2 were remarkably higher in HNSCC (p < 0.0001), which independently implies poor OS (CAV1: HR: 1.146, p = 0.027; CAV2: HR: 1.408, p = 0.002). Co-expressed genes (PXN, ITGA3, TES, and MET) were identified and analyzed by FunRich with CAV1 and CAV2, revealing a significant correlation with focal adhesion (p < 0.001), which has a vital influence on cancer progression. GSEA also showed cellular protein catabolic process (ES = 0.42) and proteasome complex (ES = 0.72), which is a key degradation system for proteins involved in oxidatively damaging and cell cycle and transcription, closely correlated with high expression of CAV2 in HNSCC. More importantly, we found the relationship between different immune cell infiltration degrees in the immune micro-environment in HNSCC and expression levels of CAV1/CAV2 (p < 0.0001). Gene-drug interaction network was checked via CTD. Moreover, tissue microarrays verified higher expression levels of CAV1/CAV2 in HNSCC (p < 0.0001), and the high expression subgroup indicated significantly poorer clinical outcomes (p < 0.05). CONCLUSIONS: The results revealed that CAV1 and CAV2 are typically upregulated in HNSCC and might predict poor prognosis.
Subject(s)
Computational Biology , Head and Neck Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Prognosis , Kaplan-Meier Estimate , Head and Neck Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics , Tumor MicroenvironmentABSTRACT
Peritoneal dialysis patients are at an increased risk of Gram-positive organism infections because of disrupted skin barrier function, presence of a peritoneal catheter, and a deficient immunological system. In particular, the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections is clinically challenging. Herein, we present a case of MRSA peritonitis that showed no response to a 14-day treatment with intraperitoneal vancomycin. To overcome unresponsiveness to vancomycin, we shifted the regimen to intraperitoneal daptomycin (given every 6 h through manual peritoneal dialysate exchanges) and oral rifampin (300 mg twice daily). The peritonitis resolved without sequelae or relapse. We suggest daptomycin and rifampin as an alternative combination therapy for MRSA infections that may otherwise remain unresolved.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Daptomycin/therapeutic use , Methicillin-Resistant Staphylococcus aureus , Peritoneal Dialysis, Continuous Ambulatory , Peritonitis/drug therapy , Rifampin/therapeutic use , Staphylococcal Infections/drug therapy , Catheters, Indwelling , Drug Therapy, Combination , Female , Humans , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Middle Aged , Peritoneal Cavity , Peritonitis/diagnosis , Peritonitis/microbiology , Salvage Therapy , Staphylococcal Infections/diagnosis , Staphylococcal Infections/microbiology , Treatment OutcomeABSTRACT
Aiming at the ecological problems such as soil erosion, desertification, and salinization in the Jingnanxia-Heishanxia reach of Yellow River, the single-factorial ecological problem's sensitivity and the comprehensive ecological sensitivity of the reach were analyzed by GIS spatial analysis, grid computing and superposition, and RS image feature extraction. The results showed that the regions with medium- and high ecological sensitivities almost covered the whole study area, including the Wufo Town of Jingtai County, the Beiwan Town, Wulan Town, Mitan Town, Dongwan Town, and Santan Town of Jingyuan County, and the area between Doucheng and Hongliutan of Pingchuan District. The high, medium, and low sensitive areas should be accordingly programmed as forbidden, medium, and deep constructing areas. During the development process of regional hydropower, effective measures should be adopted to protect the ecological environment to achieve the sustainable development of the drainage area.