MicroRNA (miR)-203 and miR-205 expression patterns identify subgroups of prognosis in cutaneous squamous cell carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) is the second most widespread cancer in humans and its incidence is rising. These tumours can evolve as diseases of poor prognosis, and therefore it is important to identify new markers to better predict its clinical evolution. OBJECTIVES: We aimed to identify the expression pattern of microRNAs (miRNAs or miRs) at different stages of skin cancer progression in a panel of murine skin cancer cell lines. Owing to the increasing importance of miRNAs in the pathogenesis of cancer, we considered the possibility that miRNAs could help to define the prognosis of CSCC and aimed to evaluate the potential use of miR-203 and miR-205 as biomarkers of prognosis in human tumours. METHODS: Seventy-nine human primary CSCCs were collected at the University Hospital of Salamanca in Spain. We identified differential miRNA expression patterns at different stages of CSCC progression in a well-established panel of murine skin cancer cell lines, and then selected miR-205 and miR-203 to evaluate their association with the clinical prognosis and evolution of human CSCC. RESULTS: miR-205 was expressed in tumours with pathological features recognized as indicators of poor prognosis such as desmoplasia, perineural invasion and infiltrative growth pattern. miR-205 was mainly expressed in undifferentiated areas and in the invasion front, and was associated with both local recurrence and the development of general clinical events of poor evolution. miR-205 expression was an independent variable selected to predict events of poor clinical evolution using the multinomial logistic regression model described in this study. In contrast, miR-203 was mainly expressed in tumours exhibiting the characteristics associated with a good prognosis, was mainly present in well-differentiated zones, and rarely expressed in the invasion front. Therefore, the expression and associations of miR-205 and miR-203 were mostly mutually exclusive. Finally, using a logistic biplot we identified three clusters of patients with differential prognosis based on miR-203 and miR-205 expression, and pathological tumour features. CONCLUSIONS: miR-205 and miR-203 tended to exhibit mutually exclusive expression patterns in human CSCC. This work highlights the utility of miR-205 and miR-203 as prognostic markers in CSCC.

Identifying molecular markers associated with classification of genotypes by External Logistic Biplots.

UNLABELLED: For characterization of genetic diversity in genotypes several molecular techniques, usually resulting in a binary data matrix, have been used. Despite the fact that in Cluster Analysis (CA) and Principal Coordinates Analysis (PCoA) the interpretation of the variables responsible for grouping is not straightforward, these methods are commonly used to classify genotypes using DNA molecular markers. In this article, we present a novel algorithm that uses a combination of PCoA, CA and Logistic Regression (LR), as a better way to interpret the variables (alleles or bands) associated to the classification of genotypes. The combination of three standard techniques with some new ideas about the geometry of the procedures, allows constructing an External Logistic Biplot (ELB) that helps in the interpretation of the variables responsible for the classification or ordination. An application of the method to study the genetic diversity of four populations from Africa, Asia and Europe, using the HapMap data is included. AVAILABILITY: The Matlab code for implementing the methods may be obtained from the web site: http://biplot.usal.es.

The Biplot as a diagnostic tool of local dependence in latent class models. A medical application.

Latent class models (LCMs) can be used to assess diagnostic test performance when no reference test (a gold standard) is available, considering two latent classes representing disease or non-disease status. One of the basic assumptions in such models is that of local or conditional independence: all indicator variables (tests) are statistically independent within each latent class. However, in practice this assumption is often violated; hence, the two-LCM fits the data poorly. In this paper, we propose the use of Biplot methods to identify the conditional dependence between pairs of manifest variables within each latent class. Additionally, we propose incorporating such dependence in the corresponding latent class using the log-linear formulation of the model.

Expression of silver-stained nucleolar organizer regions is coupled to cell cycle in rat thymic cells.

To directly analyze the relationship between the expression of silver-stained nucleolar organizer regions (AgNORs) and cell proliferation, thymic cells from newborn rats were separately sorted at the G0-G1-phase and early-mid and late-mid S-phase of the cell cycle according to their DNA content. Different AgNOR-derived parameters (mean area and numbers of AgNORs per cell and mean AgNOR-particle area) were evaluated after silver staining of cytospins. A linear correlation was observed between the mean area and numbers of AgNORs per cell, both parameters increasing progressively from G0-G1-phase to early-mid and late-mid S-phase. An increase of the mean AgNOR-particle area was also seen between G0-G1 and S-phase but this was not significant along the S-phase. A bias on the selection of S-phase cells linked to intrathymic maturation can be ruled out as S-phase cells labeled with bromodeoxyuridine were found throughout the thymus, and, moreover, the analysis of the frequency distribution of nuclear area did not show a bimodal pattern. It is concluded that the expression of AgNORs--evaluated as AgNOR area/cell or AgNOR numbers/cell--is causally or indirectly coupled to DNA synthesis and, thus, AgNORs can be considered as a cell proliferation marker.

[Effects of thiopental and propofol on suppressor T lymphocyte activity and noradrenaline release]. / Efectos del tiopental y el propofol sobre la actividad T supresora linfocitaria y la liberación de noradrenalina.

The effects of thiopental and propofol on lymphocyte suppressor T activity were studied in the basal state and after 20 min, 24 hours, and 4 days of anesthesia induction in 20 patients undergoing gynaecologic surgery. Both drugs induced a decrease in lymphocyte suppressive T activity which recovered after 4 days and tended to be larger, although not significantly, with thiopental. Serum noradrenaline concentration significantly increased after two hours of propofol anesthesia and after 20 min and 2 hours of thiopental administration. These results demonstrate that the relationship between lymphocyte suppressive T activity and noradrenaline corresponds theoretically to anesthesia deepness.

Circadian variation in the distribution of cells throughout the different phases of the cell cycle in the anterior pituitary gland of adult male rats as analysed by flow cytometry.

Flow cytometric analysis of nuclei stained with propidium iodide (PI) has been used to study the distribution of cells throughout the different phases of the cell cycle in the anterior pituitary gland of adult male Sprague-Dawley rats at different times of the day. According to PI fluorescence intensity the relative numbers of cells in S phase (cells with a DNA content between that of somatic cells in interphase (2n) and that of somatic cells after duplication of the DNA prior to cell division (4n] and G2/M phase (4n) were calculated. A significant circadian rhythm was found for cells in both the S phase (P less than 0.05) and the G2/M phase (P less than 0.01). The wave of cells in S phase with a peak at the middle of the light period (14.00 h) precedes by about 6 h the wave of cells in G2/M phase (peak at 20.00 h). Most of the DNA-replicating cells were found during the early S phase at 11.00 h, advancing further up to the middle of this phase at 14.00 h. Cells were distributed homogeneously throughout the S phase at 17.00 h. These data strongly suggest that the beginning of the light period triggers a wave of cells to leave G0/G1 into S phase.