COLONOMICS - integrative omics data of one hundred paired normal-tumoral samples from colon cancer patients.

Colonomics is a multi-omics dataset that includes 250 samples: 50 samples from healthy colon mucosa donors and 100 paired samples from colon cancer patients (tumor/adjacent). From these samples, Colonomics project includes data from genotyping, DNA methylation, gene expression, whole exome sequencing and micro-RNAs (miRNAs) expression. It also includes data from copy number variation (CNV) from tumoral samples.

Targeting metastasis-initiating cells through the fatty acid receptor CD36.

The fact that the identity of the cells that initiate metastasis in most human cancers is unknown hampers the development of antimetastatic therapies. Here we describe a subpopulation of CD44 cells in human oral carcinomas that do not overexpress mesenchymal genes, are slow-cycling, express high levels of the fatty acid receptor CD36 and lipid metabolism genes, and are unique in their ability to initiate metastasis. Palmitic acid or a high-fat diet specifically boosts the metastatic potential of CD36 metastasis-initiating cells in a CD36-dependent manner.

Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers.

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach.

A 5-gene classifier from the carcinoma-associated fibroblast transcriptomic profile and clinical outcome in colorectal cancer.

Based on 108 differentially expressed genes between carcinoma-associated fibroblasts (CAFs) and paired normal colonic fibroblasts we recently reported, a 5-gene classifier for relapse prediction in Stage II/III colorectal cancer (CRC ) was developed. Its predictive value was validated in datasets GSE17538, GSE33113 and GSE14095. An additional validation was performed in a metacohort (n=317) and 142 CRC patients by means of RT-PCR.

Differences between CAFs and their paired NCF from adjacent colonic mucosa reveal functional heterogeneity of CAFs, providing prognostic information.

Little is known about the difference in gene expression between carcinoma-associated fibroblasts (CAFs) and paired normal colonic fibroblasts (NCFs) in colorectal cancer. Paired CAFs and NCFs were isolated from eight primary human colorectal carcinoma specimens. In culture conditions, soluble factors secreted by CAFs in the conditioned media increased clonogenicity and migration of epithelial cancer cells lines to a greater extent than did NCF.

A monotonic and prognostic genomic signature from fibroblasts for colorectal cancer initiation, progression, and metastasis.

Unlabelled: The differential gene expression patterns between normal colonic fibroblasts (NCF), carcinoma-associated fibroblasts from primary tumors (CAF-PT), and CAFs from hepatic metastasis (CAF-LM) are hypothesized to be useful for predicting relapse in primary tumors. A transcriptomic profile of NCF (n = 9), CAF-PT (n = 14), and CAF-LM (n = 11) was derived. Prediction Analysis of Microarrays (PAM) was used to obtain molecular details for each fibroblast class, and differentially expressed transcripts were used to classify patients according to recurrence status.

Identification of candidate susceptibility genes for colorectal cancer through eQTL analysis.

In this study, we aim to identify the genes responsible for colorectal cancer risk behind the loci identified in genome-wide association studies (GWAS). These genes may be candidate targets for developing new strategies for prevention or therapy. We analyzed the association of genotypes for 26 GWAS single nucleotide polymorphisms (SNPs) with the expression of genes within a 2 Mb region (cis-eQTLs).

Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer.

Background: A colorectal tumor is not an isolated entity growing in a restricted location of the body. The patient's gut environment constitutes the framework where the tumor evolves and this relationship promotes and includes a complex and tight correlation of the tumor with inflammation, blood vessels formation, nutrition, and gut microbiome composition. The tumor influence in the environment could both promote an anti-tumor or a pro-tumor response.

Integrating gene expression and epidemiological data for the discovery of genetic interactions associated with cancer risk.

Dozens of common genetic variants associated with cancer risk have been identified through genome-wide association studies (GWASs). However, these variants only explain a modest fraction of the heritability of disease. The missing heritability has been attributed to several factors, among them the existence of genetic interactions (G × G).

Clinical value of prognosis gene expression signatures in colorectal cancer: a systematic review.

Introduction: The traditional staging system is inadequate to identify those patients with stage II colorectal cancer (CRC) at high risk of recurrence or with stage III CRC at low risk. A number of gene expression signatures to predict CRC prognosis have been proposed, but none is routinely used in the clinic. The aim of this work was to assess the prediction ability and potential clinical usefulness of these signatures in a series of independent datasets.

Cancer develops, progresses and responds to therapies through restricted perturbation of the protein-protein interaction network.

The products of genes mutated or differentially expressed in cancer tend to occupy central positions within the network of protein-protein interactions, or the interactome network. Integration of different types of gene and protein relationships has considerably increased the understanding of the mechanisms of carcinogenesis, while also enhancing the applicability of expression signatures. In this scenario, however, it remains unknown how cancer develops, progresses and responds to therapies in a potentially controlled manner at the systems level.

Tools for protein-protein interaction network analysis in cancer research.

As cancer is a complex disease, the representation of a malignant cell as a protein-protein interaction network (PPIN) and its subsequent analysis can provide insight into the behaviour of cancer cells and lead to the discovery of new biomarkers. The aim of this review is to help life-science researchers without previous computer programming skills to extract meaningful biological information from such networks, taking advantage of easy-to-use, public bioinformatics tools. It is structured in four parts: the first section describes the pipeline of consecutive steps from network construction to biological hypothesis generation.

Exploring the link between germline and somatic genetic alterations in breast carcinogenesis.

Recent genome-wide association studies (GWASs) have identified candidate genes contributing to cancer risk through low-penetrance mutations. Many of these genes were unexpected and, intriguingly, included well-known players in carcinogenesis at the somatic level. To assess the hypothesis of a germline-somatic link in carcinogenesis, we evaluated the distribution of somatic gene labels within the ordered results of a breast cancer risk GWAS.

Adherence to the Mediterranean diet and risk of coronary heart disease in the Spanish EPIC Cohort Study.

No known cohort study has investigated whether the Mediterranean diet can reduce incident coronary heart disease (CHD) events in a Mediterranean population. This study examined the relation between Mediterranean diet adherence and risk of incident CHD events in the 5 Spanish centers of the European Prospective Investigation into Cancer and Nutrition. Analysis included 41,078 participants aged 29-69 years, recruited in 1992-1996 and followed up until December 2004 (mean follow-up:10.

Biological convergence of cancer signatures.

Gene expression profiling has identified cancer prognostic and predictive signatures with superior performance to conventional histopathological or clinical parameters. Consequently, signatures are being incorporated into clinical practice and will soon influence everyday decisions in oncology. However, the slight overlap in the gene identity between signatures for the same cancer type or condition raises questions about their biological and clinical implications.

Biological processes, properties and molecular wiring diagrams of candidate low-penetrance breast cancer susceptibility genes.

Background: Recent advances in whole-genome association studies (WGASs) for human cancer risk are beginning to provide the part lists of low-penetrance susceptibility genes. However, statistical analysis in these studies is complicated by the vast number of genetic variants examined and the weak effects observed, as a result of which constraints must be incorporated into the study design and analytical approach. In this scenario, biological attributes beyond the adjusted statistics generally receive little attention and, more importantly, the fundamental biological characteristics of low-penetrance susceptibility genes have yet to be determined.

Changes in food supply in Mediterranean countries from 1961 to 2001.

Objective: To describe geographical differences and time trends in the supply of the most important food components of the traditional Mediterranean diet.

Design: Food supply data collected from national food balance sheets for the period 1961-2001.

Setting: Selected Mediterranean countries: Spain, Italy, France, Greece, Algeria, Morocco, Tunisia and Turkey.