A review of machine learning methods for cancer characterization from microbiome data.

Recent studies have shown that the microbiome can impact cancer development, progression, and response to therapies suggesting microbiome-based approaches for cancer characterization. As cancer-related signatures are complex and implicate many taxa, their discovery often requires Machine Learning approaches. This review discusses Machine Learning methods for cancer characterization from microbiome data.

A metatranscriptomics strategy for efficient characterization of the microbiome in human tissues with low microbial biomass.

The high background of host RNA poses a major challenge to metatranscriptome analysis of human samples. Hence, metatranscriptomics has been mainly applied to microbe-rich samples, while its application in human tissues with low ratio of microbial to host cells has yet to be explored. Since there is no computational workflow specifically designed for the taxonomic and functional analysis of this type of samples, we propose an effective metatranscriptomics strategy to accurately characterize the microbiome in human tissues with a low ratio of microbial to host content.

E-cadherin variants associated with oral facial clefts trigger aberrant cell motility in a REG1A-dependent manner.

Background: Germline mutations of E-cadherin contribute to hereditary diffuse gastric cancer (HDGC) and congenital malformations, such as oral facial clefts (OFC). However, the molecular mechanisms through which E-cadherin loss-of-function triggers distinct clinical outcomes remain unknown. We postulate that E-cadherin-mediated disorders result from abnormal interactions with the extracellular matrix and consequent aberrant intracellular signalling, affecting the coordination of cell migration.

Gastric Cancer: The Microbiome Beyond Helicobacter pylori.

Gastric cancer remains an important global health burden. Helicobacter pylori is the major etiological factor in gastric cancer, infecting the stomach of almost half of the population worldwide. Recent progress in microbiome research offered a new perspective on the complexity of the microbial communities of the stomach.

Machine learning-based approaches for cancer prediction using microbiome data.

Emerging evidence of the relationship between the microbiome composition and the development of numerous diseases, including cancer, has led to an increasing interest in the study of the human microbiome. Technological breakthroughs regarding DNA sequencing methods propelled microbiome studies with a large number of samples, which called for the necessity of more sophisticated data-analytical tools to analyze this complex relationship. The aim of this work was to develop a machine learning-based approach to distinguish the type of cancer based on the analysis of the tissue-specific microbial information, assessing the human microbiome as valuable predictive information for cancer identification.

Harnessing the Microbiome to Reduce Pancreatic Cancer Burden.

Pancreatic cancer mortality is expected to rise in the next decades. This aggressive malignancy has a dismal prognosis due to late diagnosis and resistance to treatment. Increasing evidence indicates that host-microbiome interactions play an integral role in pancreatic cancer development, suggesting that harnessing the microbiome might offer promising opportunities for diagnostic and therapeutic interventions.

The Role of the Microbiota in Esophageal Cancer.

Esophageal cancer is a major health problem, being the seventh most incidence cancer worldwide. Due to the often-late diagnosis and lack of efficient treatments, the overall 5-year survival is as low as 10%. Therefore, understanding the etiology and the mechanisms that drive the development of this type of cancer could improve the management of patients, increasing the chance of achieving a better clinical outcome.

Helicobacter pylori infection induces abnormal expression of pro-angiogenic gene ANGPT2 and miR-203a in AGS gastric cell line.

Helicobacter pylori colonizes the stomach and induces an inflammatory response that can develop into gastric pathologies including cancer. The infection can alter the gastric vasculature by the deregulation of angiogenic factors and microRNAs. In this study, we investigate the expression level of pro-angiogenic genes (ANGPT2, ANGPT1, receptor TEK), and microRNAs (miR-135a, miR-200a, miR-203a) predicted to regulate those genes, using H.

Engineered liposomes to deliver nucleic acid mimics in Escherichia coli.

Antisense oligonucleotides (ASOs) composed of nucleic acid mimics (NAMs) monomers are considered as potential novel therapeutic drugs against bacterial infections. However, bacterial envelopes are generally impermeable to naked oligonucleotides. Herein, liposomes loaded with NAMs-modified oligonucleotides (LipoNAMs) were evaluated to deliver ASOs in Escherichia coli.

Activation of Laminin γ2 by Helicobacter pylori Promotes Invasion and Survival of Gastric Cancer Cells With E-Cadherin Defects.

Background: Helicobacter pylori infection induces cellular phenotypes relevant for cancer progression, namely cell motility and invasion. We hypothesized that the extracellular matrix (ECM) could be involved in these deleterious effects.

Methods: Microarrays were used to uncover ECM interactors in cells infected with H.

The Tissue-Associated Microbiota in Colorectal Cancer: A Systematic Review.

The intestinal microbiome is associated with colorectal cancer. Although the mucosal microbiota better represents an individual's local microbiome, studies on the colorectal cancer microbiota mainly reflect knowledge obtained from fecal samples. This systematic review aimed to summarize the current evidence on the relationship between the mucosal-associated bacterial microbiota and colorectal cancer.

Proteomic Identification of a Gastric Tumor ECM Signature Associated With Cancer Progression.

The extracellular matrix (ECM) plays an undisputable role in tissue homeostasis and its deregulation leads to altered mechanical and biochemical cues that impact cancer development and progression. Herein, we undertook a novel approach to address the role of gastric ECM in tumorigenesis, which remained largely unexplored. By combining decellularization techniques with a high-throughput quantitative proteomics approach, we have performed an extensive characterization of human gastric mucosa, uncovering its composition and distribution among tumor, normal adjacent and normal distant mucosa.

Integrin β1 orchestrates the abnormal cell-matrix attachment and invasive behaviour of E-cadherin dysfunctional cells.

Background: Tumour progression relies on the ability of cancer cells to penetrate and invade neighbouring tissues. E-cadherin loss is associated with increased cell invasion in gastric carcinoma, and germline mutations of the E-cadherin gene are causative of hereditary diffuse gastric cancer. Although E-cadherin dysfunction impacts cell-cell adhesion, cell dissemination also requires an imbalance of adhesion to the extracellular matrix (ECM).

The influence of the gastric microbiota in gastric cancer development.

Colonization of the stomach by Helicobacter pylori is the trigger for a series of gastric mucosal changes that culminate in gastric cancer. Infection with this bacterium is considered the major risk factor for this malignancy. The introduction of high-throughput sequencing technologies coupled to advanced computational pipelines offered an improved understanding of the microbiome, and it is now currently accepted that, besides H.

Helicobacter pylori lipopolysaccharide structural domains and their recognition by immune proteins revealed with carbohydrate microarrays.

The structural diversity of the lipopolysaccharides (LPSs) from Helicobacter pylori poses a challenge to establish accurate and strain-specific structure-function relationships in interactions with the host. Here, LPS structural domains from five clinical isolates were obtained and compared with the reference strain 26695. This was achieved combining information from structural analysis (GC-MS and ESI-MS) with binding data after interrogation of a LPS-derived carbohydrate microarray with sequence-specific proteins.

Gastric Microbiome Diversities in Gastric Cancer Patients from Europe and Asia Mimic the Human Population Structure and Are Partly Driven by Microbiome Quantitative Trait Loci.

The human gastrointestinal tract harbors approximately 100 trillion microorganisms with different microbial compositions across geographic locations. In this work, we used RNASeq data from stomach samples of non-disease (164 individuals from European ancestry) and gastric cancer patients (137 from Europe and Asia) from public databases. Although these data were intended to characterize the human expression profiles, they allowed for a reliable inference of the microbiome composition, as confirmed from measures such as the genus coverage, richness and evenness.

Evaluation of the Use of Formalin-Fixed and Paraffin-Embedded Archive Gastric Tissues for Microbiota Characterization Using Next-Generation Sequencing.

Large numbers of well-characterized clinical samples are fundamental to establish relevant associations between the microbiota and disease. Formalin-fixed and paraffin-embedded (FFPE) tissues are routinely used and are widely available clinical materials. Since current approaches to study the microbiota are based on next-generation sequencing (NGS) targeting the bacterial 16S rRNA gene, our aim was to evaluate the feasibility of FFPE gastric tissues for NGS-based microbiota characterization.

Impact of Host DNA and Sequencing Depth on the Taxonomic Resolution of Whole Metagenome Sequencing for Microbiome Analysis.

The amount of host DNA poses a major challenge to metagenome analysis. However, there is no guidance on the levels of host DNA, nor on the depth of sequencing needed to acquire meaningful information from whole metagenome sequencing (WMS). Here, we evaluated the impact of a wide range of amounts of host DNA and sequencing depths on microbiome taxonomic profiling using WMS.

Helicobacter pylori Infection, the Gastric Microbiome and Gastric Cancer.

After a long period during which the stomach was considered as an organ where microorganisms could not thrive, Helicobacter pylori was isolated in vitro from gastric biopsies, revolutionising the fields of Microbiology and Gastroenterology. Since then, and with the introduction of high-throughput sequencing technologies that allowed deep characterization of microbial communities, a growing body of knowledge has shown that the stomach contains a diverse microbial community, which is different from that of the oral cavity and of the intestine. Gastric cancer is a heterogeneous disease that is the end result of a cascade of events arising in a small fraction of patients colonized with H.

Phenotypic heterogeneity of hereditary diffuse gastric cancer: report of a family with early-onset disease.

Background And Aims: The time course for the development of clinically significant hereditary diffuse gastric cancer (HDGC) is unpredictable. Little is known about the progression from preclinical, indolent lesions to widely invasive, aggressive phenotypes. Gastroendoscopy often fails to detect early lesions, and risk-reducing/prophylactic total gastrectomy (PTG) is the only curative approach.

Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota.

Objective: Gastric carcinoma development is triggered by . Chronic infection leads to reduced acid secretion, which may allow the growth of a different gastric bacterial community. This change in the microbiome may increase aggression to the gastric mucosa and contribute to malignancy.

Helicobacter pylori vacA Genotypes in Chronic Gastritis and Gastric Carcinoma Patients from Macau, China.

Helicobacter pylori is the major triggering factor for gastric carcinoma, but only a small proportion of infected patients develop this disease. Differences in virulence observed among H. pylori strains, namely in the vacuolating cytotoxin vacA gene, may contribute to this discrepancy.

Helicobacter pylori Activates Matrix Metalloproteinase 10 in Gastric Epithelial Cells via EGFR and ERK-mediated Pathways.

Helicobacter pylori colonizes the human stomach and increases the risk for peptic ulcer disease and gastric carcinoma. H. pylori upregulates the expression and activity of several matrix metalloproteinases (MMPs) in cell lines and in the gastric mucosa.