Claudin-Low Breast Cancer Inflammatory Signatures Support Polarization of M1-Like Macrophages with Protumoral Activity.

We previously reported that triple-negative breast cancer (BRCA) cells overexpress the cytokines GM-CSF, G-CSF, MCP-1, and RANTES, and when monocytes were 3-D co-cultured with them, M1-like macrophages were generated with the ability to induce aggressive features in luminal BRCA cell lines. These include upregulation of mesenchymal and stemness markers and invasion. In this study, we stimulated peripheral blood monocytes with the four cytokines and confirmed their capacity to generate protumoral M1-like macrophages. Using the METABRIC BRCA database, we observed that GM-CSF, MCP-1, and RANTES are associated with triple-negative BRCA and reduced overall survival, particularly in patients under 55 years of age. We propose an extended M1-like macrophage proinflammatory signature connected with these three cytokines. We found that the extended M1-like macrophage signature coexists with monocyte/macrophage, Th1 immune response, and immunosuppressive signatures, and all are enriched in claudin-low BRCA samples, and correlate with reduced patient overall survival. Furthermore, we observed that all these signatures are also present in mesenchymal carcinomas of the colon (COAD) and bladder (BLCA). The claudin-low tumor subtype has an adverse clinical outcome and remains poorly understood. This study places M1 macrophages as potential protumoral drivers in already established cancers, and as potential contributors to claudin-low aggressiveness and poor prognosis.

Erratum: A proposed method for the relative quantification of levels of circulating microRNAs in the plasma of gastric cancer patients.

[This corrects the article DOI: 10.3892/ol.2017.5816.].

A proposed method for the relative quantification of levels of circulating microRNAs in the plasma of gastric cancer patients.

Gastric cancer (GC) is the fifth most common type of malignancy and the third leading cause of cancer-associated mortality worldwide. It is necessary to identify novel methods aimed at improving the early diagnosis and treatment of GC. MicroRNA expression profiles in the plasma of patients with GC have demonstrated a potential use in the opportune diagnosis of this neoplasm. However, there are currently no standardized targets for use in the normalization of microRNA Cq values for different neoplasms. The present study tested two normalization approaches while analyzing plasma derived from patients with GC and non-atrophic gastritis. The first method utilized a panel of small nucleolar RNAs (snoRNAs) and a small nuclear RNA (snRNA) provided by a commercial array. The second normalization approach involved the use of hsa-miR-18a-5p and hsa-miR-29a-3p, which were identified by a stability analysis of the samples being tested. The results revealed that the snoRNAs and snRNA were not expressed in all samples tested. Only the stable microRNAs allowed a narrow distribution of the data and enabled the identification of specific downregulation of hsa-miR-200c-3p and hsa-miR-26b-5p in patients with GC. hsa-miR-200c-3p and hsa-miR-26b-5p have been previously linked to cancer, and a Kyoto Encyclopedia of Genes and Genomes analysis demonstrated that these microRNAs were associated with cell adhesion, cell cycle and cancer pathways.

MicroRNAs in hereditary diffuse gastric cancer.

In 2012, gastric cancer (GC) was the third cause of mortality due to cancer in men and women. In Central and South America, high mortality rates have been reported. A total of 95% of tumors developed in the stomach are of epithelial origin; thus, these are denominated adenocarcinomas of the stomach. Diverse classification systems have been established, among which two types of GC based on histological type and growth pattern have been described as follows: Intestinal (IGC) and diffuse (DGC). Approximately 1-3% of GC cases are associated with heredity. Hereditary-DGC (HDGC), with 80% penetrance, is an autosomal-type, dominant syndrome in which 40% of cases are carriers of diverse mutations of the CDH1 gene, which encodes for the cadherin protein. By contrast, microRNA are non-encoded, single-chain RNA molecules. These molecules regulate the majority of cellular functions at the post-transcriptional level. However, analysis of these interactions by means of Systems Biology has allowed the understanding of complex and heterogeneous diseases, such as cancer. These molecules are ubiquitous; however, their expression can be specific in different tissues either temporarily or permanently, depending on the stage of the cell. Due to the participation of microRNA in the processes of cellular proliferation, cell cycle control, apoptosis, differentiation and metabolism, these have been indicated to have a role in the development of cancerous processes, finding specific patterns of expression in different neoplasms, including GC, in which the microRNA expression profile is different in samples of non-cancerous versus cancerous tissues. A difference has been observed in the expression patterns of DGC and IGC. However, the role of microRNA in HDGC has not yet been established. The present study reviews the investigations that describe the participation of microRNA in the regulation of genes CDH1, RHOA, CTNNA1, INSR and TGF-ß in different neoplasms, such as HDGC.