PATRI, a Genomics Data Integration Tool for Biomarker Discovery.

The availability of genomic datasets in association with clinical, phenotypic, and drug sensitivity information represents an invaluable source for potential therapeutic applications, supporting the identification of new drug sensitivity biomarkers and pharmacological targets. Drug discovery and precision oncology can largely benefit from the integration of treatment molecular discriminants obtained from cell line models and clinical tumor samples; however this task demands comprehensive analysis approaches for the discovery of underlying data connections. Here we introduce PATRI (Platform for the Analysis of TRanslational Integrated data), a standalone tool accessible through a user-friendly graphical interface, conceived for the identification of treatment sensitivity biomarkers from user-provided genomics data, associated with information on sample characteristics. PATRI streamlines a translational analysis workflow: first, baseline genomics signatures are statistically identified, differentiating treatment sensitive from resistant preclinical models; then, these signatures are used for the prediction of treatment sensitivity in clinical samples, via random forest categorization of clinical genomics datasets and statistical evaluation of the relative phenotypic features. The same workflow can also be applied across distinct clinical datasets. The ease of use of the PATRI tool is illustrated with validation analysis examples, performed with sensitivity data for drug treatments with known molecular discriminants.

miR-30e* is an independent subtype-specific prognostic marker in breast cancer.

BACKGROUND: Breast cancer clinical outcome is affected by tumor molecular features, and the identification of subtype-specific prognostic biomarkers is relevant for breast cancer translational research. Gene expression signatures proved to be able to complement prognostic information provided by classical clinico-pathological features. Recently, microRNAs (miRNAs) have been causally linked to tumorigenesis and cancer progression and have been associated with patient outcome, also in breast cancer. METHODS: MicroRNAs associated with the development of distant metastasis were identified in a cohort of 92 ESR1+/ERBB2- lymph node-negative breast cancers from patients not receiving adjuvant treatment. Results were confirmed and further investigated in a total of 1246 miRNA and gene expression profiles of the Molecular Taxonomy of Breast Cancer International Consortium data set. Moderated t-test, univariable and multivariable Cox regression models were used for statistical analyses. RESULTS: miR-30e* was identified as independent protective prognostic factor in lymph node-negative untreated patients with ESR1+/ERBB2- tumours and retained a significant association with a good prognosis in treated patients with the same tumor subtype as well as in the ERBB2+ subtype, but not in ESR1-/ERBB2- tumours. CONCLUSIONS: We highlighted a relevant and subtype-specific role in breast cancer for miR-30e* and demonstrated that adding miRNA markers to gene signatures and clinico-pathological features can help for a better prognostication.

miR-205 regulates basement membrane deposition in human prostate: implications for cancer development.

The basement membrane (BM) is a layer of specialized extracellular matrix that surrounds normal prostate glands and preserves tissue integrity. Lack or discontinuity of the BM is a prerequisite for tumor cell invasion into interstitial spaces, thus favoring metastasis. Therefore, BM maintenance represents a barrier against cancer development and progression. In the study, we show that miR-205 participates in a network involving ΔNp63α, which is essential for maintenance of the BM in prostate epithelium. At the molecular level, ΔNp63α is able to enhance miR-205 transcription by binding to its promoter, whereas the microRNA can post-transcriptionally limit the amount of ΔNp63α protein, mostly by affecting ΔNp63α proteasomal degradation rather than through a canonical miRNA/target interaction. Functionally, miR-205 is able to control the deposition of laminin-332 and its receptor integrin-ß4. Hence, pathological loss of miR-205, as widely observed in prostate cancer, may favor tumorigenesis by creating discontinuities in the BM. Here we demonstrate that therapeutic replacement of miR-205 in prostate cancer (PCa) cells can restore BM deposition and 3D organization into normal-like acinar structures, thus hampering cancer progression.

[Mediterranean anemia in 124 Sicilian pregnant women]. / Informazione sull'anemia mediterranea in 124 puerpere siciliane.

INTRODUCTION AND AIMS: The aim of this study was to verify knowledge of beta-thalassemia in a group of Sicilian puerpere. METHODS: The study was performed in a group of 124 pregnant women chosen at random from 2769 who gave birth in 1995 in the third trimester of pregnancy at the Specialised Maternity Hospital of Santo Bambino in Catania. RESULTS: A total of 124 puerpere replied to the questionnaire out of 124 interviewed. Their age ranged from 15 to 46 years old; the most frequent age group was 20-35 years old (81 cases-65.4%). 69.3% (86 cases) were married, 5.6% (7 cases) were separated or divorced, 24.9% (31 cases) were single or living with partners. The level of education was mainly lower (39.6%-49 cases) and upper (26.6%-33 cases) secondary school; there were few cases of illiteracy (3.2%-4 cases). The women were predominantly workers (25%-31 cases), employees (37.1%-41 cases) and in 14.4% (18 cases) neither of the couple worked. 4% (5 cases) of women lived alone. 73.3% (91 cases) reported that they knew what Mediterranean anemia was, 85% (35 cases) had recently spoken about this pathology with their doctor, 57.2% (71 cases) with their gynecologist. 36.2% (45 cases) knew the meaning of hemoglobinophoresis. 25% (31 cases) replied in the affirmative to the question regarding the hemoglobinophoresis test, 28.5% (35 cases) were unable to answer and 46.7% (58 cases) replied negatively. 11.2% (14 cases) of the puerperae had been informed about this disease when they were under 20, 39.5% (49 cases) between 20 and 35 years old, and 0.80% (1 case) after 36 years old. 36.2% of those interviewed (45 cases) responded correctly to the question "when does a carrier of Mediterranean anemia risk producing children suffering from a severe blood pathology?".