TRANSCRIPTIONAL SIGNATURES OF FIELD CANCERIZATION IN GASTRIC CANCER

  • Author
  • Jessica Manoelli Costa da Silva
  • Co-authors
  • Williams Barra , Ronald Matheus da Silva Mourão , Daniel de Souza Avelar Costa , Diego Pereira , Valeria Cristiane Santos da Silva , Rubem Silva , Samia Demachki , Fabiano Cordeiro Moreira , Paulo Pimentel de Assumpção
  • Abstract
  • Introduction: Gastric cancer (GC) remains one of the most prevalent and lethal malignancies worldwide, particularly in regions like Pará, Brazil. While histopathological classifications, such as those by Lauren and the WHO, provide valuable clinical guidance, they do not fully capture the molecular complexity of GC. An often-overlooked aspect is the use of peritumoral tissue as a reference for normality, despite mounting evidence that these areas may already harbor early molecular changes. The field cancerization theory posits that histologically normal tissues adjacent to tumors can exhibit early transcriptional alterations, playing a pivotal role in early carcinogenesis. Objectives: To identify transcriptional alterations shared between tumor and peritumoral tissues but absent in healthy gastric mucosa, characterize their biological relevance, and assess their prognostic value in gastric cancer. Methods: RNA-seq data from 72 paired tumor and peritumoral samples (CAAE:47580121.9.0000.5634) and 68 normal gastric tissues (PRJNA1054173) were analyzed. A deep autoencoder with dense ReLU-activated layers was trained over 800 epochs. SHAP (SHapley Additive exPlanations) was applied to identify genes with the highest relevance to each tissue type. Coexpression patterns were assessed in tumor and peritumoral contexts. Functional network analysis was performed using the STRING database. Prognostic value was evaluated using two approaches: (i) Kaplan–Meier analysis from public GC cohorts (KM Plotter), and (ii) internal survival analysis of 46 patients from the Pará cohort using the survminer R package. Results: SHAP-based selection yielded 10,609 relevant genes for tumor and 9,483 for peritumoral tissues, with 8,871 shared genes. Among these, 138 genes showed stable expression between tumor and peritumoral tissues (Wilcoxon p > 0.9), but were differentially expressed compared to normal samples (|log2FC| > 1; adj. p < 0.05), suggesting early molecular establishment in the transformation field. From these, three COSMIC-listed cancer driver genes—FAT4, MDM4, and NDRG1—were highlighted. FAT4 (LFC = 2.00), linked to Hippo signaling, was overexpressed in tumors; MDM4 (LFC = 1.71), a p53 inhibitor, may promote genomic instability; and NDRG1 (LFC = ?2.00), a known EMT suppressor, was repressed. STRING network analysis revealed mitochondrial and metabolic enrichment among the 138 genes, with the three drivers displaying low connectivity, supporting their role as phenotypic transition regulators. Coexpression analysis showed a negative correlation between FAT4 and NDRG1 in tumors (r = ?0.36), absent in peritumoral tissue (r = +0.07), and a positive correlation between FAT4 and MDM4 only in peritumoral samples (r = +0.35). Public survival data indicated that high expression of FAT4 and MDM4 was significantly associated with poor prognosis (HR = 1.43; p < 0.001), whereas NDRG1 was not. Internally, in the study cohort (n = 46), high expression of MDM4 was also associated with worse overall survival (p = 0.013), while FAT4 and NDRG1 showed no significant association. Conclusion: These results reinforce that peritumoral tissue represents a molecularly active transitional field in gastric carcinogenesis. FAT4 and MDM4 emerge as potential markers of early transformation and poor prognosis.

  • Keywords
  • Field Cancerization, Gastric Adenocarcinoma, Deep learning
  • Modality
  • Pôster
  • Subject Area
  • Molecular Studies
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It is with great enthusiasm that we present the Annals of the Oncology International Symposium 2025, an event that continues to solidify its significance in the oncology landscape of northern Brazil. Held in Belém, Pará, Oncology 2025 centered around the theme "The cancer control challenge: better knowing it to best facing it," dedicating itself to exploring the latest frontiers in cancer treatment and prevention.

This year, the symposium provided a deep dive into the essential role of knowledge in the fight against cancer, presenting new perspectives and scientific advancements across various areas of oncology. Renowned global experts gathered to share their most recent research and innovative approaches, offering participants a comprehensive view of the challenges faced by healthcare professionals and patients worldwide.

Presentations and discussions during the event focused on critical topics such as the use of new technologies, advancements in personalized therapies, and more effective prevention strategies. Additionally, particular attention was given to the unique challenges faced by the Amazon region, with efforts aimed at developing region-specific solutions to meet local needs.

Beyond being a high-caliber academic event, Oncology 2025 stood out as a moment for integration and professional networking, with the warm hospitality of the city of Belém offering participants a unique experience. This event became a platform for exchanging ideas, where science, culture, and humanity came together in pursuit of a common goal: to improve cancer control both in Brazil and globally.

This collection of abstracts and articles presented during the event reflects the ongoing dedication to research and the development of innovative solutions, highlighting the importance of collaboration and shared knowledge in the fight against cancer.

General Submission Guidelines:

The presenting author, who does not have to be the first author, must be registered for Oncology 2025.
Each abstract may have up to 10 authors, including the main author and co-authors.
Only original, unpublished work will be accepted.
Submissions must be related to oncology. However, project descriptions, work proposals, experience reports, and literature reviews will not be considered.
Clinical case reports are allowed, provided the abstract addresses scientific questions, details clinical observations, and includes primary scientific data.
The abstract must be written in English, but presentations may be given in Portuguese.
Abstracts must be between 300 and 500 words.

  • Molecular Studies
  • Experimental Research or Clinical Research
  • Case Report or Epidemiology
  • Others

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See Annals of Oncology 2023 at:

https://www.even3.com.br/anais/oncology-2023-international-symposium/