Cancer-associated fibroblasts (CAFs) gene signatures predict outcomes in breast and prostate tumor patients.

BACKGROUND: Over the last two decades, tumor-derived RNA expression signatures have been developed for the two most commonly diagnosed tumors worldwide, namely prostate and breast tumors, in order to improve both outcome prediction and treatment decision-making. In this context, molecular signatures gained by main components of the tumor microenvironment, such as cancer-associated fibroblasts (CAFs), have been explored as prognostic and therapeutic tools. Nevertheless, a deeper understanding of the significance of CAFs-related gene signatures in breast and prostate cancers still remains to be disclosed. METHODS: RNA sequencing technology (RNA-seq) was employed to profile and compare the transcriptome of CAFs isolated from patients affected by breast and prostate tumors. The differentially expressed genes (DEGs) characterizing breast and prostate CAFs were intersected with data from public datasets derived from bulk RNA-seq profiles of breast and prostate tumor patients. Pathway enrichment analyses allowed us to appreciate the biological significance of the DEGs. K-means clustering was applied to construct CAFs-related gene signatures specific for breast and prostate cancer and to stratify independent cohorts of patients into high and low gene expression clusters. Kaplan-Meier survival curves and log-rank tests were employed to predict differences in the outcome parameters of the clusters of patients. Decision-tree analysis was used to validate the clustering results and boosting calculations were then employed to improve the results obtained by the decision-tree algorithm. RESULTS: Data obtained in breast CAFs allowed us to assess a signature that includes 8 genes (ITGA11, THBS1, FN1, EMP1, ITGA2, FYN, SPP1, and EMP2) belonging to pro-metastatic signaling routes, such as the focal adhesion pathway. Survival analyses indicated that the cluster of breast cancer patients showing a high expression of the aforementioned genes displays worse clinical outcomes. Next, we identified a prostate CAFs-related signature that includes 11 genes (IL13RA2, GDF7, IL33, CXCL1, TNFRSF19, CXCL6, LIFR, CXCL5, IL7, TSLP, and TNFSF15) associated with immune responses. A low expression of these genes was predictive of poor survival rates in prostate cancer patients. The results obtained were significantly validated through a two-step approach, based on unsupervised (clustering) and supervised (classification) learning techniques, showing a high prediction accuracy (≥ 90%) in independent RNA-seq cohorts. CONCLUSION: We identified a huge heterogeneity in the transcriptional profile of CAFs derived from breast and prostate tumors. Of note, the two novel CAFs-related gene signatures might be considered as reliable prognostic indicators and valuable biomarkers for a better management of breast and prostate cancer patients.

Big data analytics and smart cities: applications, challenges, and opportunities.

Urban environments continuously generate larger and larger volumes of data, whose analysis can provide descriptive and predictive models as valuable support to inspire and develop data-driven Smart City applications. To this aim, Big data analysis and machine learning algorithms can play a fundamental role to bring improvements in city policies and urban issues. This paper introduces how Big Data analysis can be exploited to design and develop data-driven smart city services, and provides an overview on the most important Smart City applications, grouped in several categories. Then, it presents three real-case studies showing how data analysis methodologies can provide innovative solutions to deal with smart city issues. The first one is an approach for spatio-temporal crime forecasting (tested on Chicago crime data), the second one is methodology to discover mobility hotsposts and trajectory patterns from GPS data (tested on Beijing taxi traces), the third one is an approach to discover predictive epidemic patterns from mobility and infection data (tested on real COVID-19 data). The presented real-world cases prove that data analytics models can effectively support city managers in tackling smart city challenges and improving urban applications.

Epidemic forecasting based on mobility patterns: an approach and experimental evaluation on COVID-19 Data.

During an epidemic, decision-makers in public health need accurate predictions of the future case numbers, in order to control the spread of new cases and allow efficient resource planning for hospital needs and capacities. In particular, considering that infectious diseases are spread through human-human transmissions, the analysis of spatio-temporal mobility data can play a fundamental role to enable epidemic forecasting. This paper presents the design and implementation of a predictive approach, based on spatial analysis and regressive models, to discover spatio-temporal predictive epidemic patterns from mobility and infection data. The experimental evaluation, performed on mobility and COVID-19 data collected in the city of Chicago, is aimed to assess the effectiveness of the approach in a real-world scenario.