Cancer Stem Cell Markers-Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis.

Cancer stem cells (CSCs) may contribute to an increased risk of recurrence in ovarian cancer (OC). Further research is needed to identify associations between CSC markers and OC patients' clinical outcomes with greater certainty. If they prove to be correct, in the future, the CSC markers can be used to help predict survival and indicate new therapeutic targets. This study aimed to determine the CSC markers at mRNA and protein levels and their association with clinical presentation, outcome, and risk of recurrence in HGSOC (High-Grade Serous Ovarian Cancer). TCGA (The Cancer Genome Atlas) database with 558 ovarian cancer tumor samples was used for the evaluation of 13 CSC markers (ALDH1A1, CD44, EPCAM, KIT, LGR5, NES, NOTCH3, POU5F1, PROM1, PTTG1, ROR1, SOX9, and THY1). Data on mRNA and protein levels assessed by microarray and mass spectrometry were retrieved from TCGA. Models to predict chemotherapy response and survival were built using multiple variables, including epidemiological data, expression levels, and machine learning methodology. ALDH1A1 and LGR5 mRNA expressions indicated a higher platinum sensitivity (p = 3.50 × 10-3; p = 0.01, respectively). POU5F1 mRNA expression marked platinum-resistant tumors (p = 9.43 × 10-3). CD44 and EPCAM mRNA expression correlated with longer overall survival (OS) (p = 0.043; p = 0.039, respectively). THY1 mRNA and protein levels were associated with worse OS (p = 0.019; p = 0.015, respectively). Disease-free survival (DFS) was positively affected by EPCAM (p = 0.004), LGR5 (p = 0.018), and CD44 (p = 0.012). In the multivariate model based on CSC marker expression, the high-risk group had 9.1 months longer median overall survival than the low-risk group (p < 0.001). ALDH1A1, CD44, EPCAM, LGR5, POU5F1, and THY1 levels in OC may be used as prognostic factors for the primary outcome and help predict the treatment response.

Occurrence of integrons and antibiotic resistance genes in cryoconite and ice of Svalbard, Greenland, and the Caucasus glaciers.

The prevalence of integrons and antibiotic resistance genes (ARGs) is a serious threat for public health in the new millennium. Although commonly detected in sites affected by strong anthropogenic pressure, in remote areas their occurrence, dissemination, and transfer to other ecosystems is poorly recognized. Remote sites are considered as a benchmark for human-induced contamination on Earth. For years glaciers were considered pristine, now they are regarded as reservoirs of contaminants, thus studies on contamination of glaciers, which may be released to other ecosystems, are highly needed. Therefore, in this study we evaluated the occurrence and frequency of clinically relevant ARGs and resistance integrons in the genomes of culturable bacteria and class 1 integron-integrase gene copy number in the metagenome of cryoconite, ice and supraglacial gravel collected on two Arctic (South-West Greenland and Svalbard) and two High Mountain (the Caucasus) glaciers. Altogether, 36 strains with intI1 integron-integrase gene were isolated. Presence of class 1 integron-integrase gene was also recorded in metagenomic DNA from all sampling localities. The mean values of relative abundance of intI1 gene varied among samples and ranged from 0.7% in cryoconite from Adishi Glacier (the Caucasus) to 16.3% in cryoconite from Greenland. Moreover, antibiotic-resistant strains were isolated from all regions. Genes conferring resistance to ß-lactams (blaSHV, blaTEM, blaOXA, blaCMY), fluoroquinolones (qepA, qnrC), and chloramphenicol (cat, cmr) were detected in the genomes of bacterial isolates.