Biology subjects

Avelar, D. d. S.

Publications and source records attributed to Avelar, D. d. S..

7 recordsLinked to original sources

bioRxiv2025

Transcriptomic Mutational Profiling of Gastric Adenocarcinoma in Northern Brazil

Gastric cancer (GC) remains among the neoplasms with the worst prognosis, partly due to its biological heterogeneity and the scarcity of robust biomarkers. The characterization of mutational profiles from transcripts can reveal specific tumor signatures and point to therapeutic targets. This study investigated the landscape of mutations expressed in 102 samples of gastric adenocarcinoma from northern Brazil, which were sequenced using NGS. Readings were aligned to the reference genome using STAR (two-pass mode), and variants were called with GATK and VarDict. Annotations and impact predictions were generated using VEP, SIFT, and PolyPhen. We identified >90,000 variants; among the most frequently mutated genes, FTH1 stood out. The mutational profile was described using maftools, and signatures were inferred with MutationalPatterns. We observed a predominant distribution of SNVs, with C>T transitions as the most common event, in addition to patterns compatible with signatures related to replication damage and DNA repair. To mitigate biases inherent to RNA-seq, we applied filters for coverage, strand bias, and RNA editing hotspots. Together, the data outline a regional landscape of mutations expressed in GC and reinforce the usefulness of the transcriptome for prioritizing biomarkers and functional hypotheses that may guide genomic validations and subsequent clinical studies.

bioinformatics↗

bioRxiv2025

Interspecies Functional Divergence: The Microbiome's Role in FLOT Response e Across Gastric Cancer Subtypes

BackgroundGastric adenocarcinoma exhibits marked molecular and histological heterogeneity, which is reflected in distinct patterns of progression, therapeutic response, and prognosis. Although the FLOT regimen (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) represents the current standard for perioperative chemotherapy, its systemic effects on the tumor microenvironment, including the associated bacterial microbiome and host gene expression, remain poorly understood. MethodsThis study investigated the effects of FLOT on the functional and ecological structure of intestinal and diffuse subtype gastric tumors by assessing its simultaneous influence on the human transcriptome, the bacterial transcriptome, and inter-kingdom interactions. We analyzed 55 tumor samples (37 intestinal subtype; 18 diffuse subtype) and explored potential genetic-functional interactions between the bacterial microbiome and the human genome. ResultsThe results reveal a highly specific functional pattern in the diffuse subtype, absent in the intestinal subtype, demonstrating a unique ecological-transcriptional plasticity mediated by the microbiota under chemotherapeutic pressure. The interaction network was dominated by high-magnitude positive correlations. Notably, the bacterial gene leuS showed a robust association with the human gene HCN1 and processes such as potassium ion transmembrane transport, membrane depolarization, and regulation of postsynaptic membrane potential, indicating a coordinated activation of ion channels and neuroepithelial circuits. Bacterial species including Bacteroides uniformis, Faecalibacterium prausnitzii, Butyrivibrio crossotus, Prevotella copri, and Simiaoa sunii also converged functionally on HCN1. Additionally, bacterial genes mfd, nifJ, secY, rplF, and tet(Q) were associated with pathways related to cell adhesion, epithelial proliferation, membrane potential control, and synaptic transduction. DiscussionIntegrative analysis reveals that the FLOT regimen acts as a systemic remodeler of the gastric tumor microenvironment, exerting distinct effects according to the histological subtype. While the intestinal subtype responds more aligned with the cytotoxic goals of chemotherapy, the diffuse subtype exhibits a functional plasticity that favors the emergence of adaptive and possibly pro-tumoral phenotypes. We propose a mechanistic model where in chemotherapy selectively reshapes the microbial ecosystem, which in turn modulates host functional circuits, directly influencing tumor behavior. These findings open perspectives for combined therapeutic strategies that include targeted modulation of the microbiome as an adjuvant to chemotherapy.

cancer biology↗

bioRxiv2025

FERROPTOSIS GENE SIGNATURES REVEAL DISTINCT REGULATORY LANDSCAPES IN GASTRIC ADENOCARCINOMA AND OTHER TISSUES

BackgroundGastric adenocarcinoma (GAC) remains one of the most lethal malignancies worldwide, with late-stage diagnosis and limited therapeutic options. Ferroptosis, a regulated form of cell death driven by iron-dependent lipid peroxidation, has emerged as a promising target for overcoming tumor resistance mechanisms. This study aimed to characterize the transcriptional landscape of ferroptosis-related genes in GAC, comparing tumor, peritumoral, metaplastic, and normal gastric tissues. MethodsRNA-Seq was performed on 385 biopsied samples from patients treated at the Joao de Barros Barreto University Hospital. Differential expression analysis was conducted using DESeq2, and genes related to ferroptosis were identified based on FerrDb V2 annotations. Visualization included volcano plots, DAPC clustering, heatmaps, and gene dominance scoring. ResultsGAC samples showed a distinct ferroptotic expression signature, with simultaneous upregulation of key promoters (e.g., CDKN2A, NOX4, EGFR, IL6) and suppressors (e.g., HSPB1, SCD, NUPR1, GDF15). Notably, the tumor tissue exhibited a net dominance of ferroptosis-inhibitory genes, suggesting an adaptive response to oxidative stress. Adjacent tissues showed partial overlap with tumor profiles, while metaplastic tissue displayed a hybrid signature with selective suppression of ferroptosis. Normal mucosa exhibited dominant expression of promoters, contrasting with the tumors anti-ferroptotic phenotype. ConclusionThe transcriptional heterogeneity and regulatory imbalance of ferroptosis-related genes in GAC support its role as a potential therapeutic axis. These findings provide molecular insights for biomarker discovery and ferroptosis-targeted strategies in gastric cancer.

cancer biology↗

bioRxiv2025

Viral Landscape of Gastric Adenocarcinoma Reveals Clinically Relevant Viruses

BackgroundGastric cancer (GC) ranks among the most common and lethal cancers worldwide, with poor prognosis mainly due to late diagnosis. Accumulating evidence highlights the role of the gastric microbiome in carcinogenesis through inflammation, genomic instability, and immune modulation. Unlike the bacterial component, the gastric virome remains largely unexplored despite its potential contribution to tumor development. The present study aimed to characterize the virome present in tumor and peritumoral tissues from patients with GC. Materials and Methods105 tumor and 85 peritumoral gastric tissues were analyzed. RNA was extracted, libraries were prepared, and sequencing was performed on the Illumina NextSeq 500. Viral reads were classified with Kraken2. Taxonomic profiles, viral abundance and diversity metrics were computed in R, with group differences assessed by Wilcoxon tests and PERMANOVA (p < 0.05). ResultsIn this study, 38 viral orders and 329 viral genera were identified in gastric tumor and peritumoral tissues. Tumor tissues harbored 210 viral genera, including 109 exclusive to this microenvironment, with bacteriophages comprising the majority, alongside human-infecting and other eukaryotic viruses. Lymphocryptovirus, Cytomegalovirus, and Alphapapillomavirus were enriched in tumors. Alpha and beta diversity analyses revealed no significant differences between tumor and peritumoral tissues, indicating comparable viral richness and composition. ConclusionThese findings underscore the complexity of the gastric virome and provide a foundation for future investigations into the interactions and mechanisms through which the viral community could influence the development of gastric cancer, highlighting its potential role in gastric health and disease.

genetics↗

bioRxiv2025

Treasure: A Sensitive Pipeline for Species-Level and Functional Microbiome Profiling

Next Generation Sequencing (NGS) methods, such as 16S rRNA amplicon sequencing and Whole Genome Sequencing (WGS), enable taxonomic analyses but have limitations. This project proposes the development of a computational tool capable of performing functional analysis of the most abundant microorganisms within a microbiome based on taxonomic analysis. The proposed method integrates the tools Kraken, Gffread, and Salmon. Compared to Samsa 2, a commonly used pipeline for RNA-Seq Total samples, the new approach demonstrated superior performance across all evaluated scenarios (p < 0.01). The tool aims to functionally characterize the microbiome of regions affected by Gastric Cancer (GC) and adjacent areas, assess associations between survival, expression/abundance, and identify potential microbial biomarkers for GC.

bioinformatics↗

bioRxiv2025

Characterization of Human Endogenous Retroviruses in Gastric Cancer with Helicobacter pylori: A Study from Northern Brazil

Human endogenous retroviruses (HERVs) are retroelements that have integrated their genetic material into the human genome, accumulating mutations over time and accounting for approximately 8% of the genome. Under abnormal deregulation conditions, these elements can be expressed and contribute to the development of diseases, such as gastric cancer. This malignancy may be associated with infections, including those caused by Helicobacter pylori. However, the scientific literature does not yet provide clear evidence regarding the relationship between HERVs and H. pylori in the context of gastric cancer. Thus, HERVs may represent potential biomarkers for this neoplasm, as well as possible therapeutic targets. This study aimed to characterize HERV expression in gastric cancer using next-generation sequencing (NGS). We analyzed 46 tumor tissue samples and 42 peritumoral tissue samples from patients diagnosed with gastric adenocarcinoma, collected at HUJBB and Ophir Loyola hospitals. Among the tumor samples, 38 tested positive for H. pylori infection. For library preparation, 1 g of total RNA per sample was used, with integrity assessed via TapeStation ([~]260 bp band). cDNA libraries were sequenced using the Illumina NextSeq 500 platform (paired-end), following the ID Output V2 kit protocol. Alignment was performed with STAR software, and HERVs were identified and quantified using Telescope. Differential expression analysis of HERVs was performed on transcript data using DESeq2. A total of 183 HERVs were found to be differentially expressed in tumor tissues compared to adjacent tissues. In tumor samples associated with H. pylori infection, 44 HERVs showed differential expression. Overall, tumor tissues exhibited higher HERV transcription compared to adjacent tissues.

genetics↗

bioRxiv2025

Unmasking Epstein-Barr Role in Gastric Carcinogenesis: A Gene Expression Approach to Virus-Positive Tumors

Human gammaherpesvirus 4 or Epstein-Barr virus (EBV) is an oncogenic virus linked to malignancies like gastric adenocarcinoma. Notably, EBV infection induces genetic and epigenetic modifications that play a crucial role in oncogenesis and tumor progression, underscoring the importance of analyzing viral gene expression in the context of gastric cancer (GC) to elucidate its unique characteristics. This study aimed to perform a molecular characterization of EBV gene expression using next-generation sequencing (NGS). The analysis included human gene expression patterns in EBV-positive and EBV-negative samples and the expression of viral genes in EBV-positive samples. The study received approval from the Ethics and Research Committee of Joao de Barros Barreto University Hospital under reference number 47580121.9.0000.5634. It utilized 76 tumor tissue samples from patients with gastric cancer who had undergone surgical resection, and both fresh and paraffin-embedded samples were gathered for total RNA sequencing (RNA-seq) and in situ hybridization (ISH). The RNA-seq was conducted in a pair-end manner on the NextSeq(R) platform (Illumina(R), US). The NextSeq(R) 500 MID Output V2 kit - 150 cycles (Illumina(R)) were utilized following the manufacturers instructions. ISH targeting RNA-1 of EBER1 (Y5200, DAKO, Carpinteria) was performed using the automated Dako system. Molecular characterization was conducted using the Kraken2 software. Subsequently, to elucidate the mechanisms through which EBV may influence gastric cancer, we analyzed the patterns of human gene expression in EBV-positive and EBV-negative samples. Of the 76 samples, 8 were classified as EBV-positive according to the applied methodology. Our analysis identified approximately 834 differentially expressed genes, 92 of which exhibited an AUC > 0.85. These genes are implicated in tumor progression, cellular metabolism, and both innate and adaptive immune responses. Additionally, viral genes expressed in the positive samples were evaluated, and we found manifestations of both lytic phase and latent phase genes. Finally, our study presents an efficient strategy for molecular classification of EBV-positive gastric cancer based on NGS and shows the effects of EBV on human gene expression. Author summaryIn our study, we explored how EBV influences the development of stomach cancer. EBV is a virus known to be linked to various cancers, including gastric cancer, and it can alter the behavior of both human and viral genes within infected cells. To investigate this, we analyzed tissue samples from 76 patients with stomach cancer, focusing on differences between samples with and without EBV. Using advanced sequencing technology, we identified over 800 genes that behave differently in EBV-positive cancers. These genes are involved in critical processes like how cells grow, how the immune system responds, and how energy is produced within cells. We also examined which EBV genes were active in the cancer samples and found evidence of both dormant and active phases of the virus. Our work demonstrated how EBV may contribute to stomach cancer and suggests new ways to classify and understand this disease. By uncovering these details, we hope to pave the way for more targeted treatments in the future.

cancer biology↗