DeepHP: A New Gastric Mucosa Histopathology Dataset for Helicobacter pylori Infection Diagnosis.

Emerging deep learning-based applications in precision medicine include computational histopathological analysis. However, there is a lack of the required training image datasets to generate classification and detection models. This phenomenon occurs mainly due to human factors that make it difficult to obtain well-annotated data. The present study provides a curated public collection of histopathological images (DeepHP) and a convolutional neural network model for diagnosing gastritis. Images from gastric biopsy histopathological exams were used to investigate the performance of the proposed model in detecting gastric mucosa with Helicobacter pylori infection. The DeepHP database comprises 394,926 histopathological images, of which 111 K were labeled as Helicobacter pylori positive and 283 K were Helicobacter pylori negative. We investigated the classification performance of three Convolutional Neural Network architectures. The models were tested and validated with two distinct image sets of 15% (59K patches) chosen randomly. The VGG16 architecture showed the best results with an Area Under the Curve of 0.998%. The results showed that CNN could be used to classify histopathological images from gastric mucosa with marked precision. Our model evidenced high potential and application in the computational pathology field.

Genetic and Transcriptional Analysis of 8q24.21 Cluster in Gastric Cancer.

BACKGROUND/AIM: Previous studies from our research group have shown that trisomy 8 and the amplification of the 8q24.21 region is very frequent in gastric cancer (GC). Little is known about the role of most genes located in this region. Thus, the aim of this study was to understand the possible impact of transcriptional alterations and copy number variation (CNV) of four genes located in the 8q24.21 region - FAM49B, FAM84B, GSDMC and miR-5194 - in GC. MATERIALS AND METHODS: Fifty-one to 85 matched pairs of tumoral and adjacent non-tumoral gastric tissues, from patients with primary GC, were used to analyze gene expression and CNV of the selected genes. We also included 29 H. pylori negative and gastritis negative gastric mucosa tissues from individuals without cancer obtained by endoscopy, as control samples. RESULTS: The expression of FAM49B, GSDMC and miR-5194 was higher in both tumoral and adjacent non-tumoral samples compared to the negative control. The expression of FAM84B showed no significant difference between tumoral samples and negative controls. However, the expression of FAM84B in the adjacent non-tumoral samples was higher compared to negative control and tumoral samples. Moreover, the higher expression of GSDMC was associated with T3 and T4 tumors, with tumors on stage III and IV and with advanced tumors. Higher copy numbers of FAM49B and GSDMC were associated with intestinal tumor type and with moderately or well-differentiated tumors. Higher copy number of FAM84B was associated with moderately or well-differentiated tumors. Furthermore, the expression of all four genes was positively correlated. CONCLUSION: All four genes are upregulated in GC and may play an important role in these neoplasms. GSDMC expression was associated with more aggressive tumors.

Triple-Negative Breast Cancer circRNAome Reveals Hsa_circ_0072309 as a Potential Risk Biomarker.

Circular RNAs (circRNAs) are a class of long non-coding RNAs that have the ability to sponge RNA-Binding Proteins (RBPs). Triple-negative breast cancer (TNBC) has very aggressive behavior and poor prognosis for the patient. Here, we aimed to characterize the global expression profile of circRNAs in TNBC, in order to identify potential risk biomarkers. For that, we obtained RNA-Seq data from TNBC and control samples and performed validation experiments using FFPE and frozen tissues of TNBC patients and controls, followed by in silico analyses to explore circRNA-RBP interactions. We found 16 differentially expressed circRNAs between TNBC patients and controls. Next, we mapped the RBPs that interact with the top five downregulated circRNAs (hsa_circ_0072309, circ_0004365, circ_0006677, circ_0008599, and circ_0009043) and hsa_circ_0000479, resulting in a total of 16 RBPs, most of them being enriched to pathways related to cancer and gene regulation (e.g., AGO1/2, EIF4A3, ELAVL1, and PTBP1). Among the six circRNAs, hsa_circ_0072309 was the one that presented the most confidence results, being able to distinguish TNBC patients from controls with an AUC of 0.78 and 0.81, respectively. This circRNA may be interacting with some RBPs involved in important cancer-related pathways and is a novel potential risk biomarker of TNBC.

Behavioral and Neuropathological Changes After Toxoplasma gondii Ocular Conjunctival Infection in BALB/c Mice.

Ocular infection with Toxoplasma gondii causes toxoplasmosis in mice. However, following ocular infection with tachyzoites, the cause of the accompanying progressive changes in hippocampal-dependent tasks, and their relationship with the morphology and number of microglia, is less well understood. Here, in 6-month-old, female BALB/c mice, 5 µl of a suspension containing 48.5 × 106 tachyzoites/ml was introduced into the conjunctival sac; control received an equal volume of saline. Before and after instillation, all mice were subject to an olfactory discrimination (OD) test, using predator (cat) feces, and to an open-field (OF) task. After the behavioral tests, the animals were culled at either 22 or 44 days post-instillation (dpi), and the brains and retinas were dissected and processed for immunohistochemistry. The total number of Iba-1-immunolabeled microglia in the molecular layer of the dentate gyrus was estimated, and three-dimensional reconstructions of the cells were evaluated. Immobility was increased in the infected group at 12, 22, and 43 dpi, but the greatest immobility was observed at 22 dpi and was associated with reduced line crossing in the OF and distance traveled. In the OD test, infected animals spent more time in the compartment with feline fecal material at 14 and at 43 dpi. No OD changes were observed in the control group. The number of microglia was increased at 22 dpi but returned to control levels by 44 dpi. These changes were associated with the differentiation of T. gondii tachyzoites into bradyzoite-enclosed cysts within the brain and retina. Thus, infection of mice with T. gondii alters exploratory behavior, gives rise to a loss in predator's odor avoidance from 2 weeks after infection, increased microglia number, and altered their morphology in the molecular layer of the dentate gyrus.

Association of Androgenic Regulation and MicroRNAs in Acinar Adenocarcinoma of Prostate.

BACKGROUND: Prostate cancer represents 3.8% of cancer deaths worldwide. For most prostate cancer cells to grow, androgens need to bind to a cellular protein called the androgen receptor (AR). This study aims to demonstrate the expression of five microRNAs (miRs) and its influence on the AR formation in patients from the northern region of Brazil. MATERIAL AND METHODS: Eighty-four tissue samples were investigated, including nodular prostatic hyperplasia (NPH) and acinar prostatic adenocarcinoma (CaP). Five miRs (27a-3p, 124, 130a, 488-3p, and 506) were quantified using the TaqMan® Real Time PCR method and AR was measured using Western blotting. RESULTS: Levels of miRs 124, 130a, 488-3p, and 506 were higher in NPH samples. Conversely, in the CaP cases, higher levels of miR 27a-3p and AR were observed. CONCLUSION: In the future, these microRNAs may be tested as markers of CaP at the serum level. The relative expression of AR was 20% higher in patients with prostate cancer, which suggests its potential as a biomarker for prostate malignancy.

CircRNAs as Potential Blood Biomarkers and Key Elements in Regulatory Networks in Gastric Cancer.

Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of cancer death in the world. It is a disease that encompasses a variety of molecular alterations, including in non-coding RNAs such as circular RNAs (circRNAs). In the present study, we investigated hsa_circ_0000211, hsa_circ_0000284, hsa_circ_0000524, hsa_circ_0001136 and hsa_circ_0004771 expression profiles using RT-qPCR in 71 gastric tissue samples from GC patients (tumor and tumor-adjacent samples) and volunteers without cancer. In order to investigate the suitability of circRNAs as minimally invasive biomarkers, we also evaluated their expression profile through RT-qPCR in peripheral blood samples from patients with and without GC (n = 41). We also investigated the predicted interactions between circRNA-miRNA-mRNA and circRNA-RBP using the KEGG and Reactome databases. Overall, our results showed that hsa_circ_0000211, hsa_circ_0000284 and hsa_circ_0004771 presented equivalent expression profiles when analyzed by different methods (RNA-Seq and RT-qPCR) and different types of samples (tissue and blood). Further, functional enrichment results identified important signaling pathways related to GC. Thus, our data support the consideration of circRNAs as new, minimally invasive biomarkers capable of aiding in the diagnosis of GC and with great potential to be applied in clinical practice.

Differential regulation of LRRC37A2 in gastric cancer by DNA methylation.

Gastric cancer (GC) is one of the leading types of fatal cancer worldwide. Epigenetic manipulation of cancer cells is a useful tool to better understand gene expression regulatory mechanisms and contributes to the discovery of novel biomarkers. Our research group recently reported a list of 83 genes that are potentially modulated by DNA methylation in GC cell lines. Herein, we further explored the regulation of one of these genes, LRRC37A2, in clinical samples. LRRC37A2 expression was evaluated by RT-qPCR, and DNA methylation was studied using next-generation bisulphite sequencing in 36 GC and paired adjacent nonneoplastic tissue samples. We showed that both reduced LRRC37A2 mRNA levels and increased LRRC37A2 exon methylation were associated with undifferentiated and poorly differentiated tumours. Moreover, LRRC37A2 gene expression and methylation levels were inversely correlated at the +45 exon CpG site. We suggest that DNA hypermethylation may contribute to reducing LRRC37A2 expression in undifferentiated and poorly differentiated GC. Therefore, our results show how some genes may be useful to stratify patients who are more likely to benefit from epigenetic therapy.Abbreviations: AR: androgen receptor; 5-AZAdC: 5-aza-2'-deoxycytidine; B2M: beta-2-microglobulin; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GC: gastric cancer; GLM: general linear model; LRRC37A2: leucine-rich repeat containing 37 member A2; SD: standard deviation; TFII-I: general transcription factor II-I; TSS: transcription start site; XBP1: X-box binding protein 1.

Acquired acoria and iris pearls in leprosy: Case report.

PURPOSE: To describe a case of a patient presenting with acquired acoria and iris pearls, a rare eye manifestation and pathognomonic finding for leprosy; to reinforce clinical, histopathological, and therapeutic aspects of ocular involvement in leprosy. METHODS: Case report. CASE DESCRIPTION: A 62-year-old male presenting with acquired acoria and iris pearls in both eyes due to leprosy also had anterior uveitis and cataract. Histopathological diagnosis of iris pearls was confirmed by the presence of Hansen's bacilli. Ophthalmological examination revealed improvement of the visual acuity after iridectomy and extracapsular cataract extraction. CONCLUSIONS: To our knowledge, this is the first reported case of acquired acoria in a leprosy patient. It led to impaired vision and reversible blindness. Proper diagnosis and ophthalmological treatment of patients with these conditions are essential for the maintenance of a good quality of life.

Gastric Cancer Microbiome.

Identifying a microbiome pattern in gastric cancer (GC) is hugely debatable due to the variation resulting from the diversity of the studied populations, clinical scenarios, and metagenomic approach. H. pylori remains the main microorganism impacting gastric carcinogenesis and seems necessary for the initial steps of the process. Nevertheless, an additional non-H. pylori microbiome pattern is also described, mainly at the final steps of the carcinogenesis. Unfortunately, most of the presented results are not reproducible, and there are no consensual candidates to share the H. pylori protagonists. Limitations to reach a consistent interpretation of metagenomic data include contamination along every step of the process, which might cause relevant misinterpretations. In addition, the functional consequences of an altered microbiome might be addressed. Aiming to minimize methodological bias and limitations due to small sample size and the lack of standardization of bioinformatics assessment and interpretation, we carried out a comprehensive analysis of the publicly available metagenomic data from various conditions relevant to gastric carcinogenesis. Mainly, instead of just analyzing the results of each available publication, a new approach was launched, allowing the comprehensive analysis of the total sample amount, aiming to produce a reliable interpretation due to using a significant number of samples, from different origins, in a standard protocol. Among the main results, Helicobacter and Prevotella figured in the "top 6" genera of every group. Helicobacter was the first one in chronic gastritis (CG), gastric cancer (GC), and adjacent (ADJ) groups, while Prevotella was the leader among healthy control (HC) samples. Groups of bacteria are differently abundant in each clinical situation, and bacterial metabolic pathways also diverge along the carcinogenesis cascade. This information may support future microbiome interventions aiming to face the carcinogenesis process and/or reduce GC risk.

Sex and FOXP3 gene rs2232365 polymorphism may be associated with the clinical and pathological aspects of chronic viral diseases.

BACKGROUND: The forkhead box protein 3 (FOXP3) transcription factor is one of the main markers of immunological suppression in different pathological profiles, and the presence of polymorphic variants may alter the gene expression of this factor. Despite descriptions of an association between the presence of the rs2232365 polymorphism and chronic diseases, the role of the sex variant in this context has not yet been elucidated, as the FOXP3 gene is located on the human sex chromosome X. RESULTS: To contribute to this topic, 323 women and 373 men were enrolled in the study, of which 101 were diagnosed with chronic viral liver diseases (39 women and 62 men), 67 with HTLV-1 infection (44 women and 23 men), 230 with coronary artery disease (91 women and 139 men) and 298 healthy and uninfected blood donors (149 women and men). They were genotyped for the rs2232365 polymorphism. The rs2232365 polymorphism was associated with clinical and pathological aspects and biomarkers of viral infections only in men, with functional differences between different infections. CONCLUSIONS: A relationship is suggested between sex and FOXP3 rs2232365 polymorphism, resulting in different biological repercussions.

Global Analyses of Expressed Piwi-Interacting RNAs in Gastric Cancer.

Gastric cancer (GC) represents a notable amount of morbidity and mortality worldwide. Understanding the molecular basis of CG will offer insight into its pathogenesis in an attempt to identify new molecular biomarkers to early diagnose this disease. Therefore, studies involving small non-coding RNAs have been widely explored. Among these, PIWI-interacting RNAs (piRNAs) are an emergent class that can play important roles in carcinogenesis. In this study, small-RNA sequencing was used to identify the global piRNAs expression profile (piRNome) of gastric cancer patients. We found 698 piRNAs in gastric tissues, 14 of which were differentially expressed (DE) between gastric cancer (GC), adjacent to gastric cancer (ADJ), and non-cancer tissues (NC). Moreover, three of these DE piRNAs (piR-48966*, piR-49145, piR-31335*) were differently expressed in both GC and ADJ samples in comparison to NC samples, indicating that the tumor-adjacent tissue was molecularly altered and should not be considered as a normal control. These three piRNAs are potential risk biomarkers for GC, especially piR-48966* and piR-31335*. Furthermore, an in-silico search for mRNAs targeted by the differentially expressed piRNAs revealed that these piRNAs may regulate genes that participate in cancer-related pathways, suggesting that these small non-coding RNAs may be directly and indirectly involved in gastric carcinogenesis.

Lymph nodes may be a source for immunetherapy in gastric cancer.

BACKGROUND: adoptive immunotherapy is a promising cancer therapy. Immune cells are capable of recognizing and destroying cancer cells and represent a powerful strategy, however, this approach remains technically complicated, due to the need to select and isolate immune cells from these, present cancer antigens to those cells, expanding and reinjecting them. Lymph nodes recovered during gastric cancer surgery may represent an option for immunotherapy, since they harbor an enormous amount of immune cells, which have already been presented to cancer antigens. The advantage of selecting only cancer-negative lymph has not been determined yet. The status of immune checkpoints in the immune cells within the lymph nodes was analyzed in order to try to solve this problem. MATERIALS AND METHODS: Tissue microarrays were constructed and automated immunostaining for PD-1 and PD-L1 was performed on 143 lymph nodes from 70 patients with gastric adenocarcinoma. RESULTS: In positive nodes, PD-L1 was only positivity in cancer cells (6%) and PD-1 was positive for B lymphocytes (60%), T lymphocytes (70%) and one case in cancer cells (2.5%). In negative nodes, most cases were positive for PD-1 in B (73.1%) and T (71.65%) lymphocytes. CONCLUSIONS: Expression of PD-1 and PD-L1 in gastric cancer lymph nodes was demonstrated for the first time. PD-1 is expressed in positive and negative nodes, which could activate the PD-1 pathway. Lymphocytes from tumor-free lymph nodes were negative for PD-L1, and this might represent an advantage for selecting these lymph nodes as a potential source of immune cells for adoptive immunotherapy.

Hepatic metastasis in Frantz's tumor: A case report.

INTRODUCTION: Frantz's Tumor or Solid Pseudopapillary Neoplasm (SPN) is rare with a solid-cystic pattern, and most common in young women. PRESENTATION OF CASE: This study based on guidelines for case reports (SCARE) reports a case of SPN in a teenager aged 13 years at the diagnosis time, attended at a teaching public hospital in Brazil, which evolved into liver metastases. Clinical, laboratory, therapeutic and imaging data were collected from the physical chart and analyzed in light of current publications on the topic. The first consultation occurred in January 2012, where weight loss, fever, vomiting, left-sided hypochondrium and epigastric pain were reported. Imaging exams evidenced an expansive heterogeneous process in the pancreatic tail; however, laboratory exams and tumor markers did not present alteration in relation to reference values. In March of 2012, she underwent caudal body pancreatectomy, splenectomy, segmental colectomy and colo-coloanastomosis as a function of the intraoperative findings. After 63 months, right-sided hepatectomy was performed to resect metastases. Currently, she is undergoing outpatient monitoring, without complaint or alterations in imaging and laboratory exams, totaling 100 months of global survival. DISCUSSION: This is an interesting case report of a rare tumor, in so far as without any adjuvant chemotherapies, an 8-year long survival time could be achieved in this particular type of tumor despite initially large tumor expansion and later liver metastases. CONCLUSION: Additional epidemiological studies, molecular and clinical trials are required to increase knowledge on SPN.

The impact of DNA demethylation on the upregulation of the NRN1 and TNFAIP3 genes associated with advanced gastric cancer.

Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Very few therapeutic options are currently available in this neoplasia. The use of 5-Aza-2'-deoxycytidine (5-AZAdC) was approved for the treatment of myelodysplastic syndromes, and this drug can treat solid tumours at low doses. Epigenetic manipulation of GC cell lines is a useful tool to better understand gene expression regulatory mechanisms for clinical applications. Therefore, we compared the gene expression profile of 5-AZAdC-treated and untreated GC cell lines by a microarray assay. Among the genes identified in this analysis, we selected NRN1 and TNFAIP3 to be evaluated for gene expression by RT-qPCR and DNA methylation by bisulfite DNA next-generation sequencing in 43 and 52 pairs of GC and adjacent non-neoplastic tissue samples, respectively. We identified 83 candidate genes modulated by DNA methylation in GC cell lines. Increased expression of NRN1 and TNFAIP3 was associated with advanced tumours (P < 0.05). We showed that increased NRN1 and TNFAIP3 expression seems to be regulated by DNA demethylation in GC samples: inverse correlations between the mRNA and DNA methylation levels in the promoter of NRN1 (P < 0.05) and the intron of TNFAIP3 (P < 0.05) were detected. Reduced NRN1 promoter methylation was associated with III/IV TNM stage tumours (P = 0.03) and the presence of Helicobacter pylori infection (P = 0.02). The identification of demethylated activated genes in GC may be useful in clinical practice, stratifying patients who are less likely to benefit from 5-AZAdC-based therapies. KEY MESSAGES: Higher expression of NRN1 and TNFAIP3 is associated with advanced gastric cancer (GC). NRN1 promoter hypomethylation contributes to gene upregulation in advanced GC. TNFAIP3 intronic-specific CpG site demethylation contributes to gene upregulation in GC. These findings may be useful to stratify GC patients who are less likely to benefit from DNA demethylating-based therapies.

NGF (-198C > T, Ala35Val) and p75NTR (Ser205Leu) gene mutations are associated with liver function in different histopathological profiles of the patients with chronic viral hepatitis in the Brazilian Amazon.

BACKGROUNDS: Neural growth factor (NGF) is a neurotrophin that can interact with the p75NTR receptor and initiate a cascade of reactions that determines cell survival or death, and both are associated with the physiology of liver tissue. Single nucleotide polymorphisms (SNPs) in the NGF and p75NTR genes have been investigated in different pathologies; however, there are no studies that have analyzed their biological roles in the hepatic microenvironment. In the present study, we evaluated the impact of SNPs in these genes on the maintenance of liver function at different stages of inflammation and fibrosis in patients with chronic viral liver disease in the Brazilian Amazon. METHODS: The SNPs -198C > T, Arg80Gln, Val72Met, Ala35Val, Ala18Ala and Ser205Leu were genotyped by real-time PCR in samples from patients with chronic viral hepatitis stratified by stage of inflammation and liver fibrosis. Histopathological, viral load (VL), liver enzyme and comorbidities data were obtained from updated medical records. Other aspects were highlighted by applied epidemiological questionnaires. RESULTS: The -198C/T and Ala35Val polymorphisms in NGF were associated with changes in histopathological profiles, VL and liver enzymes. Ser205Leu polymorphism in p75NTR was associated only with changes in VL and liver enzymes. Polymorphic frequencies were variable among different ethnic populations, mainly for biologically relevant polymorphisms. A multifactorial network of interactions has been established based on genetic, virological, behavioral and biochemical aspects. CONCLUSION: Mutations in the NGF (-198C > T, Ala35Val) and p75NTR (Ser205Leu) genes, within the list of multifactorial aspects, are associated with liver function in different histopathological profiles of patients with chronic viral liver disease in the Brazilian Amazon.

Hepatic TLR4, MBL and CRP gene expression levels are associated with chronic hepatitis C.

Contact with HCV triggers the activation of innate mechanisms responsible for initial infection control. Host cells expressed extra- or intracellularly molecules that promote recognition of pathogen-associated molecular patterns (PAMPs). Toll-like receptor 4 (TLR4), mannose-binding lectin (MBL) and C-reactive protein (CRP) are molecules available for HCV PAMP recognition. The present study evaluated TLR4, MBL and CRP gene expression in the hepatic tissue of chronic HCV carriers (n = 22) and the association of that expression with the pathogenesis of HCV as well as the progression of liver fibrosis. Liver biopsy specimens from the HCV group were divided according to the METAVIR classification: without fibrosis and/or mild fibrosis (F0-F1), moderate fibrosis (F2), and severe fibrosis and/or cirrhosis (F3-F4) and A0-A1 (absent or mild inflammation) and A2 (moderate inflammation); normal liver samples were used as a control (n = 8). The mRNA levels of the genes studied were quantified by real-time PCR, and plasma CRP and liver enzymes were measured using an automated system. CRP and MBL expression was significantly lower in the HCV group compared to that in the control group (p < .0001 and p = .0242, respectively). TLR4 expression was higher in the HCV group than in the control group (p = .0448) and was also significantly higher (p = .0314) with lower levels of necroinflammatory activity (A0-A1), with a significant correlation between the expression of MBL with TLR4 as well as a positive correlation between plasma levels and CRP expression in the HCV group (p = .0431). Hepatic TLR4, MBL and CRP expression showed no significant association with liver enzymes nor plasma viral load. Mechanisms of HCV escape seem to influence hepatic TLR4, MBL and CRP expression, resulting in a change in the transcription profile of these proteins of innate immunity, which may contribute to virus persistence, liver fibrogenesis and loss of normal liver function.

The Small Bowel Cancer Incidence Enigma.

Although the small bowel is a vast organ with a highly proliferative epithelium, the incidence of small bowel cancers is surprisingly low. Many factors could be involved in this unexpected cancer incidence, including difficult access to the exploration of the small bowel mucosa, which might lead to missed diagnoses of non-obstructive and non-bleeding small tumours. Moreover, possible factors that influence the low incidence include more efficient machinery of DNA replication and DNA repair enzymes, peculiarities in microbiota components, competence of the immune system, and the speed of intestinal transit. Importantly, the answer for the enigmatic risk of driver mutations caused by replication errors may be hidden in the small bowel, which is an obscure part of digestive tract that is usually inaccessible by endoscopic or colonoscopic conventional investigations. These observations warrant the necessity of an urgent exploration of small bowel features, including the evaluation of DNA replication controls and expression of DNA repair genes, in order to shed light on these obscure events.

Whole mitochondrial genome sequencing highlights mitochondrial impact in gastric cancer.

Mitochondria are organelles that perform major roles in cellular operation. Thus, alterations in mitochondrial genome (mtGenome) may lead to mitochondrial dysfunction and cellular deregulation, influencing carcinogenesis. Gastric cancer (GC) is one of the most incident and mortal types of cancer in Brazil, particularly in the Amazon region. Here, we sequenced and compared the whole mtGenome extracted from FFPE tissue samples of GC patients (tumor and internal control - IC) and cancer-free individuals (external control - EC) from this region. We found 3-fold more variants and up to 9-fold more heteroplasmic regions in tumor when compared to paired IC samples. Moreover, tumor presented more heteroplasmic variants when compared to EC, while IC and EC showed no significant difference when compared to each other. Tumor also presented substantially more variants in the following regions: MT-RNR1, MT-ND5, MT-ND4, MT-ND2, MT-DLOOP1 and MT-CO1. In addition, our haplogroup results indicate an association of Native American ancestry (particularly haplogroup C) to gastric cancer development. To the best of our knowledge, this is the first study to sequence the whole mtGenome from FFPE samples and to apply mtGenome analysis in association to GC in Brazil.

Disparities in Epidemiological Profile of Gastric Adenocarcinoma in Selected Cities of Brazil

Background: Despite decreasing global incidence trends, gastric cancer is still among the five most incident cancers in the world and the third cancer-related cause of death. In Brazil, differences in incidence and mortality exist depending on the geographic region studied. Objective: To describe the incidence, mortality, trends and age-period-cohort of gastric cancer in three cities of Brazil (Sao Paulo, Belem and Fortaleza), in the period 1990-2012. Mortality for gastric cancer in Brazil overall and by region was described. Methods: 33,462 incident cases of gastric cancer were identified from the population-based cancer registries and 23,424 deaths from mortality information system in residents of the three cities and in Brazil were included in the study. Data for incident cases were extracted from the Population Based Cancer Registries from the National Cancer Institute (INCA). Mortality data on gastric cancer were extracted from Information Technology Department of Brazilian Public Health Care System/Health Ministry (DATASUS/MS). Mortality and incidence age standardized rates were calculated. For trends analysis the Joinpoint Regression and age-period-cohort model were applied. Results: Belem presented the highest incidence rates for gastric adenocarcinoma. Decreasing incidence trends were identified in Sao Paulo (-7.8% in men; -6.3% in women) and in Fortaleza (-1.2% in men). Increasing incidence trends were observed for women in Belem (1.8%) and Fortaleza (1.1%). In Belem (Amazon area), there was an increased risk for gastric cancer in women born after the 1960s. Overall in Brazil mortality for gastric cancer is decreasing. Mortality trends showed significant reduction, for both sexes, in the three Brazilian cities. Conclusion: Incidence of gastric cancer is increasing in women born in the sixties in Belem (Amazon region) and Fortaleza (Northeast region). In Brazil there was increase in mortality in Northeast region and decrease in others regions. More update data on incidence for Amazon and Northeast region is needed.

miRNome Reveals New Insights Into the Molecular Biology of Field Cancerization in Gastric Cancer.

BACKGROUND: MicroRNAs (miRNAs) play an important role in gastric carcinogenesis and have been associated with gastric field cancerization; however, their role is not fully understood in this process. We performed the miRNome sequencing of non-cancerous, adjacent to tumor and gastric cancer samples to understand the involvement of these small RNAs in gastric field cancerization. METHODS: We analyzed samples of patients without cancer as control (non-cancerous gastric samples) and adjacent to cancer and gastric cancer paired samples, and considered miRNAs with |log2(fold change)| > 2 and Padj < 0.05 to be statistically significant. The identification of target genes, functional analysis and enrichment in KEGG pathways were realized in the TargetCompare, miRTargetLink, and DAVID tools. We also performed receiver operating characteristic (ROC) curves and miRNAs that had an AUC > 0.85 were considered to be potential biomarkers. RESULTS: We found 14 miRNAs exclusively deregulated in gastric cancer, of which six have potential diagnostic value for advanced disease. Nine miRNAs with known tumor suppressor activities (TS-miRs) were deregulated exclusively in adjacent tissue. Of these, five have potential diagnostic value for the early stages of gastric cancer. Functional analysis of these TS-miRs revealed that they regulate important cellular signaling pathways (PI3K-Akt, HIF-1, Ras, Rap1, ErbB, and MAPK signaling pathways), that are involved in gastric carcinogenesis. Seven miRNAs were differentially expressed in both gastric cancer and adjacent regarding to non-cancerous tissues; among them, hsa-miR-200a-3p and hsa-miR-873-5p have potential diagnostic value for early and advanced stages of the disease. Only hsa-miR-196a-5p was differentially expressed between adjacent to cancer and gastric cancer tissues. In addition, the other miRNAs identified in this study were not differentially expressed between adjacent to cancer and gastric cancer, suggesting that these tissues are very similar and that share these molecular changes. CONCLUSION: Our results show that gastric cancer and adjacent tissues have a similar miRNA expression profile, indicating that studied miRNAs are intimately associated with field cancerization in gastric cancer. The overexpression of TS-miRs in adjacent tissues may be a barrier against tumorigenesis within these pre-cancerous conditions prior to the eventual formation or relapse of a tumor. Additionally, these miRNAs have a great accuracy in discriminating non-cancerous from adjacent to tumor and cancer tissues and can be potentially useful as biomarkers for gastric cancer.