Biology subjects

Assumpcao, P. P.

Publications and source records attributed to Assumpcao, P. P..

13 recordsLinked to original sources

bioRxiv2025

Transcriptional Signatures of Field Cancerization in Gastric Cancer

The high rate of local recurrence in gastric adenocarcinoma (GA) suggests that carcinogenesis is not a focal event but a field-wide process. This phenomenon, known as "field cancerization," posits that histologically normal peritumoral tissue is, in fact, a pre-neoplastic field harboring incipient molecular alterations that confound genomic studies using it as a normal control. To overcome this limitation, we performed a three-way comparative transcriptomic analysis of tumor, peritumoral, and true-normal gastric tissues using a deep learning framework. We identified a stable 138-gene signature established within the peritumoral field and conserved in the tumor, which was absent in healthy controls. Within this signature, three key COSMIC-listed driver genes were highlighted: the Hippo pathway component FAT4 and the p53-inhibitor MDM4 were upregulated, while the EMT-suppressor NDRG1 was repressed. Co-expression analysis revealed a dynamic rewiring of these drivers, with a significant positive correlation between FAT4 and MDM4 emerging exclusively in the peritumoral field. In contrast, a negative correlation between FAT4 and NDRG1 was observed specifically in the tumor context. In public cohorts, high expression of FAT4 and MDM4 was significantly associated with poor patient prognosis, whereas NDRG1 showed no prognostic association. Critically, the prognostic power of MDM4 was validated in our local patient cohort. Our findings demonstrate that the peritumoral field is a molecularly distinct state in gastric carcinogenesis, characterized by a metabolic shift, and identify FAT4 and MDM4 as key drivers of this early transition, with significant potential as prognostic biomarkers.

genetics↗

bioRxiv2025

Dietary Patterns and Gene Expression Profiles in Gastric Adenocarcinoma Patients from the Northern Region of Brazil

BackgroundGastric adenocarcinoma (GA) remains a major public health concern worldwide, with incidence influenced by demographic, socioeconomic, and lifestyle factors. Diet is a modifiable risk factor that can shape tumor biology, potentially affecting gene expression and the tumor microenvironment. Understanding how dietary patterns correlate with molecular signatures in GA may provide insights for preventive and therapeutic strategies. MethodsThis retrospective, cross-sectional, analytical study included 60 patients diagnosed with gastric adenocarcinoma and treated at the Joao de Barros Barreto University Hospital, Para, Brazil. Structured questionnaires collected sociodemographic, lifestyle (smoking and alcohol), clinical, and dietary data. Dietary patterns were analyzed according to the Brazilian Ministry of Health guidelines. A subset of 16 patients was selected for gene expression profiling to evaluate correlations between dietary exposure and molecular alterations. ResultsThe patient cohort exhibited a predominance of males (56.7%) and older adults (>60 years), often from socioeconomically disadvantaged backgrounds. Dietary analysis revealed insufficient intake of fruits, vegetables, and legumes, alongside high consumption of ultraprocessed foods, especially sugar-sweetened beverages. Gene expression analysis identified 48 differentially expressed genes between patients with lower (LEDRF) and higher (HEDRF) dietary risk exposure. Six genes with potential biological relevance were highlighted: MAGEA3, IL6, HCAR2, NLRP4, PGA3, and CTCFL. MEFDR patients showed overexpression of MAGEA3, IL6, and HCAR2, associated with cell proliferation, inflammation, and tumor microenvironment remodeling. DiscussionThe results suggest that dietary patterns may modulate gene expression and influence the tumor microenvironment in gastric adenocarcinoma. Diets rich in ultraprocessed foods and sugar may promote a pro-inflammatory and pro-oxidant microenvironment, while consumption of fruits, vegetables, and bioactive compounds appears protective, potentially regulating epigenetic, metabolic, and immunological pathways. The study underscores the importance of integrated approaches combining nutritional intervention and molecular profiling to better understand GA progression and identify potential therapeutic targets.

cancer biology↗

bioRxiv2025

Cancer-Testis Antigens as Clinical and Prognostic Biomarkers in Gastric Adenocarcinoma: Integration of Differential Expression, Clinical Associations, Survival, and Co-Expression Networks

Gastric adenocarcinoma (GAC) remains one of the leading causes of cancer-related mortality, characterized by marked molecular and clinical heterogeneity, which underscores the need for robust biomarkers. In this study, we aimed to evaluate the role of cancer-testis antigens (CTAs) in GAC through integrated analyses of differential expression, clinical associations, survival impact, and gene co-expression networks. The cohort included 156 patients with complete clinical data, comprising a total of 362 tissue samples (tumor, peritumoral, and metaplastic). We identified 541 differentially expressed genes, of which 49 corresponded to previously described CTAs. Between GAC and peritumoral tissues, 14 CTAs exhibited significant differential expression, with MAGEA3, MAGEA6, GOLGA6L1, and MAGEA2 among the most highly expressed in tumors. Relevant associations were observed between the expression of MAGEA3, MAGEA6, POTEF, and CTCFL with TNM staging, as well as IGF2BP1, DAZ1/3/4, YBX2, and PCDHA4 in relation to variables such as tumor depth, metastasis, and TCGA subtypes. Survival analysis demonstrated that high expression of IGF2BP1, CTCFL, CT45A5, and LIN28B was strongly associated with worse prognosis (HR > 2.7), whereas SYCE1L, PIK3R3, and ZNF683 showed a protective effect. The co-expression network revealed five main clusters, highlighting germline-related modules (MAGEA, DAZ, CSAG), adhesion and transcriptional regulation (YBX2, POTEF, PCDHA, TAF1L), and immune-related genes (IRAK3, CXCR1, PIK3R3), evidencing functional integration between proliferation, adhesion, and immune microenvironment modulation. Collectively, these findings reinforce CTAs as potential clinical and prognostic biomarkers in GAC, with direct implications for risk stratification and the development of personalized therapeutic strategies.

cancer biology↗

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

Integrated Expression Analysis of C-MYC Oncogene-Associated Pathways in Gastric Adenocarcinoma and its Correlation with Clinicopathological Factors

BackgroundThe C-MYC oncogene is a well-established driver of gastric carcinogenesis, yet the integrated expression pattern of its complex regulatory network and its clinical implications in gastric adenocarcinoma (GAC) remain to be fully elucidated. This study aimed to perform an integrated bioinformatic analysis of C-MYC and its associated pathways in a cohort of GAC patients to delineate its expression profile, assess its potential as a biomarker, and correlate its patterns with clinicopathological factors such as Lauren classification and neoadjuvant treatment status. MethodsThe study included transcriptome data from 74 GAC tumor samples and 68 normal gastric tissue samples. Following RNA sequencing, a comprehensive bioinformatic analysis was conducted on a curated list of 21 C-MYC-associated genes. The methodology included differential expression analysis (DESeq2), unsupervised hierarchical clustering, Principal Component Analysis (PCA), and Receiver Operating Characteristic (ROC) curve analysis to evaluate diagnostic performance. Gene expression levels were also statistically correlated with Lauren histological subtypes and neoadjuvant therapy status using the Wilcoxon rank-sum test. ResultsThe analysis revealed a profound dysregulation of the C-MYC network in GAC. While MYC itself was significantly upregulated, its transcriptional antagonists, particularly MXD4 and MXD3, were the most significantly downregulated genes. This gene signature robustly separated tumor from normal tissues in both hierarchical clustering and PCA. ROC analysis demonstrated the outstanding diagnostic potential of several genes, with MXD4 achieving a perfect Area Under the Curve (AUC) of 1.00, surpassing the diagnostic value of MYC (AUC=0.86). Stratification by Lauren classification showed that MYC and its stability regulator PTBP1 were significantly more expressed in the intestinal subtype, whereas the repressors MXD3 and MXI1 were higher in the diffuse subtype. No significant expression differences were observed based on neoadjuvant treatment status. ConclusionGastric adenocarcinoma is characterized by a coordinated dysregulation of the C-MYC network, marked by both oncogene activation and a concurrent loss of its key transcriptional repressors. The profound downregulation of antagonists like MXD4 serves as an exceptionally accurate molecular signature for GAC, suggesting its potential as a diagnostic biomarker superior to MYC alone. The divergent expression patterns between Lauren subtypes highlight distinct molecular pathobiology and may have implications for targeted therapies

genetics↗

bioRxiv2025

GASTRIC CANCER BASED ON TRANSCRIPTION FACTORS

IntroductionGastric adenocarcinoma (GA) is responsible for thousands of deaths annually and significantly affects patients quality of life. To increase knowledge about this disease, several studies have focused on the transcriptional control mechanism by analyzing the role of transcription factors (TFs) in GA. MethodsThis study identified differential expression (DE) of TFs in GA samples from 74 patients using NGS, biostatistical analysis in R, and comparison with 68 normal tissue samples in the genetic databases of the National Center for Biotechnology Information (NCBI). Results1,564 human transcription factors were DE. Of these, 87 were selected using the established cutoff value of AUC [≥] 0.95, and 25 were analyzed for their influence on GA carcinogenesis. Based on their role in biological processes, nine TFs were found to be underexpressed due to their growth suppression and cell differentiation properties, notably the TFs IRF3 and CXXC1. Sixteen TFs were overexpressed, associated with drug resistance, disease promotion, metastasis, and poor prognosis in GA, such as AHR, NCOA3, RRB1, and STAT3, respectively. ConclusionThis study integrated systematic bioinformatics and NGS, which revealed novel TFs with important oncogenic and suppressive functions in GA. Therefore, it provides new insights into genes with potential biomarkers for prognostic prediction in GA, which may offer important implications for clinical practice and may effectively target treatment, monitoring, or disease recurrence.

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

Molecular Insights into ANPEP in Gastric Adenocarcinoma

Alanyl aminopeptidase (ANPEP) has been implicated in various cancers, but its specific role in gastric adenocarcinoma (GC) remains incompletely understood. This study analyzed ANPEP gene expression in gastric cancer (GC), peritumoral tissue (PTT), metaplasia (M), and normal tissue (N). Total RNA was extracted, libraries were prepared and sequenced on the Illumina NextSeq 500. Data was processed using the nf-core/rnaseq pipeline. Transcript quantifications were imported with tximport and normalized using DESeq2. Differential expression (|log2FC| >2; adj. p < 0.05) and Kruskal-Wallis tests identified key genes. ANPEP was significantly upregulated in GC, PTT, and M compared to normal tissue (p < 0.01), suggesting its involvement in early mucosal transformation and malignant progression. Heatmap analysis revealed upregulation of genes related to immune function and oxidative stress, indicating an immunosuppressive and apoptosis-resistant tumor microenvironment. Correlation analyses identified strong positive associations between ANPEP and genes involved in cytoskeletal remodeling, immune modulation, and metabolic regulation, suggesting that ANPEP supports both the invasive potential of tumor cells and the establishment of an immunosuppressive niche. These findings position ANPEP as a promising biomarker for early detection and a candidate for targeted therapies.

cancer biology↗

bioRxiv2020

Characterization and analysis of the transcriptome in Arapaima gigas using multi-tissue RNA-sequencing

Arapaima gigas is a giant bony tongue air-breathing fish, and a promising species for aquaculture due to its particular features. However, there is still a lack of information on its biology and few transcriptome studies are available. Our aim was to characterize the transcriptome of arapaima in order to shed light on molecular networks contributing to its unique traits. Through RNA-sequencing, we generated a transcriptome from eight tissues (brain, pituitary, heart, muscle, kidney, lung, ovary, and testis) collected from arapaima adults specimens. Using a genome-guided strategy associated with homologous protein evidence, 57,706 transcripts were assembled, which aligned to 23,353 high confidence protein-coding genes. The analysis revealed a global view of expression patterns, as well as it allowed us to identify tissue-specific gene clusters, transcription factors within the clusters, and to compare expression patterns between male and female. These analyses has generated tissue-specific and sex-biased transcriptome profiles, which will be helpful to understand its molecular biology, evolution, and also guide future functional studies of the arapaima.

genomics↗

bioRxiv2020

A small interfering RNA (siRNA) database for SARS-CoV-2

Coronavirus disease 2019 (COVID-19) rapidly transformed into a global pandemic, for which a demand for developing antivirals capable of targeting the SARS-CoV-2 RNA genome and blocking the activity of its genes has emerged. In this work, we propose a database of SARS-CoV-2 targets for siRNA approaches, aiming to speed the design process by providing a broad set of possible targets and siRNA sequences. Beyond target sequences, it also displays more than 170 features, including thermodynamic information, base context, target genes and alignment information of sequences against the human genome, and diverse SARS-CoV-2 strains, to assess whether siRNAs targets bind or not off-target sequences. This dataset is available as a set of four tables in a single spreadsheet file, each table corresponding to sequences of 18, 19, 20, and 21 nucleotides length, respectively, aiming to meet the diversity of technology and expertise among labs around the world concerning siRNAs design of varied sizes, more specifically between 18 and 21nt length. We hope that this database helps to speed the development of new target antivirals for SARS-CoV-2, contributing to more rapid and effective responses to the COVID-19 pandemic.

bioinformatics↗