PIWIL1-REGULATED CANCER TESTIS ANTIGENS MAGEC3 AND MAGEA6 AS POTENTIAL TARGETS FOR ANTINEOPLASTIC IMMUNOTHERAPY

  • Author
  • Lucas Brabo Rotella
  • Co-authors
  • Jade Dias Valente , Livia Érika Carlos Marques , Thaíssa Vitória Portal Rodrigues , Taíssa Maíra Thomaz Araújo , Bruna Cláudia Meireles Khayat , Edivaldo Herculano Correa de Oliveira , Fabiano Cordeiro Moreira , Paulo Pimentel de Assumpção , André Salim Khayat
  • Abstract
  • Introduction: Cancer presents a high mortality rate, related to the biology and aggressiveness of the disease itself, but also to poor response or adverse effects related to therapy. One strategy to mitigate this problem is immunotherapy, which recognizes specific targets in neoplastic cells and induces cell death through the immune system. In the search for tumor markers, there is the possibility of identifying targets that are more highly expressed in tumors and less abundant in healthy cells. In this regard, cancer/testis antigens (CTAs) represent a group of tumor-associated antigens that are normally expressed in immune-privileged tissues, such as the testicles, but present aberrant expression in various types of cancer, especially in the more advanced stages. Functionally, CTAs are implicated in the self-renewal and differentiation of stem cells in their respective lineages. Aberrant expression profiles of CTAs are associated with cancer development and can be used as biomarkers and targets for immunotherapy. Therefore, understanding the regulation of the expression of these antigens may contribute to the understanding of the carcinogenesis process and the prediction of targets for immunotherapeutics. In this context, it is known that the PIWIL1 gene (piwi like RNA-mediated gene silencing 1) encodes a key regulatory protein in transcription and translation, with expression almost exclusively in the testicles, overexpressed in cancerous tissues, stem cells, and germ cells, but absent in normal tissues. Objectives: Thus, this study sought to investigate the possible role of PIWIL1 in modulating the expression of CTAs. Methods: For this, PIWIL1 knockout was performed by CRISPR-Cas9 in the AGP01 cell line (Metastatic Gastric Adenocarcinoma) established from cells present in ascitic fluid. The gene expression profile of AGP01 cell lines with and without PIWIL1 knockout was obtained using a microarray assay, and the data were concatenated and described through software and then subjected to Levene’s and Student’s t-tests, considering a critical alpha of 0.05. Results: PIWIL1 gene knockout was observed through the addition of seven adenines, resulting in a subsequent change of all amino acids immediately following the insertion point and a premature STOP codon. Among the differentially expressed CTAs, MAGEC3 and MAGEA6 show significant reduction in gene expression and relevant biological impact, possibly being directly or indirectly associated with the action cascade of the PIWIL1 gene. MAGEA6 acts as a ubiquitin ligase activator that functions as an autophagy repressor and can also stimulate the ubiquitination of the p53/TP53 protein and play a role in tumor transformation or aspects of tumor progression. Meanwhile, MAGEC3 exhibits antigenicity and is associated with stress-induced cell cycle arrest and reduced expression of DNA repair genes. Conclusion: Therefore, it is suggested that the two CTAs are potential candidates for antigenic immunotherapy, with a possible form of individualized treatment for patients with gastric cancer with PIWIL1 overexpression.

  • Keywords
  • PIWIL1; Gastric cancer; Cancer-testis antigens
  • 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/