{
  "abstract": "Background Age-related alterations in the tumor immune microenvironment are increasingly recognized as critical determinants of breast cancer progression and response to treatment. The phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling axis plays a central role in promoting tumor cell proliferation, immune evasion, and resistance to immunotherapy. However, limited data exist on the age-specific expression dynamics of this pathway and its regulatory components in African populations, where breast cancer disproportionately affects younger women. This study investigates age- and subtype-specific gene expression profiles of the PI3K/AKT/mTOR pathway and associated immune-modulatory and apoptotic regulators in Nigerian breast cancer patients.Methods One hundred and two (102) formalin-fixed paraffin-embedded (FFPE) breast tumor samples, including benign and malignant cases, were collected from female patients in Abuja, Nigeria. Histopathological classification was followed by immunohistochemical analysis of the expression of phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), mammalian target of rapamycin (mTOR), forkhead box O (FOXO), mouse double minute 2 homolog (MDM2), rat sarcoma proto-oncogene (RAS), phosphatase and tensin homolog (PTEN), BCL2-associated agonist of cell death (BAD), human telomerase reverse transcriptase (hTERT), tumor protein p53 (p53), breast cancer susceptibility genes 1 and 2 (BRCA1/2), nuclear factor kappa B (NF-κB), BCL2-associated X protein (BAX), GATA-binding protein 3 (GATA3), and caspase-3. Expression levels were quantified using ImageJ and analyzed based on patient age and tumor subtype.Results Distinct age-dependent gene expression patterns were observed. Middle-aged patients (40–59 years) had the highest malignancy rate (61.07%) and showed overexpression of PI3K (88.46%), mTOR (84.62%), and hTERT, indicating aggressive tumor behavior. Young adults (20–39 years) exhibited elevated expression of AKT (92.86%), PTEN (85.71%), and BRCA1/2, suggesting active oncogenic signaling with partially preserved DNA repair capacity. In contrast, older adults (60–79 years) had reduced PI3K but elevated expression of FOXO, BAD, MDM2, and BAX, reflecting immune aging and dysregulated apoptosis. Notably, p53 expression declined progressively with age. Tumor subtype analysis showed high AKT and mTOR expression in estrogen receptor/progesterone receptor-positive (ER/PR+) and human epidermal growth factor receptor 2-positive (HER2+) tumors, while triple-negative breast cancer (TNBC) subtypes exhibited upregulation of FOXO, MDM2, and GATA3 with concomitant downregulation of NF-κB, indicating distinct immunological and molecular characteristics.Conclusions This study highlights profound age- and subtype-specific heterogeneity in the expression of the PI3K/AKT/mTOR signaling pathway and associated immunomodulatory genes in Nigerian breast cancer patients. These findings underscore the urgent need for precision immunotherapeutic approaches tailored to the molecular and immune profiles of African breast cancer populations.",
  "authors": [
    {
      "affiliations": [
        "Covenant University, Ota, Ogun state, Nigeria",
        "Covenant University Public Health and Wellbeing Research Cluster (CUPHWERC), Ota, Ogun state, Nigeria"
      ],
      "name": "Magdalene ENO Udobi"
    },
    {
      "affiliations": [
        "Covenant University, Ota, Ogun state, Nigeria",
        "Covenant University Public Health and Wellbeing Research Cluster (CUPHWERC), Ota, Ogun state, Nigeria"
      ],
      "name": "Shalom Nwodo Chinedu"
    },
    {
      "affiliations": [
        "Covenant University, Ota, Ogun state, Nigeria",
        "Covenant University Public Health and Wellbeing Research Cluster (CUPHWERC), Ota, Ogun state, Nigeria"
      ],
      "name": "Israel Sunmola Afolabi"
    },
    {
      "affiliations": [
        "Nile University of Nigeria, Abuja, FCT Abuja, Nigeria",
        "Asokoro District Hospital, Abuja, FCT, Nigeria, Asokoro, FCT Abuja, Nigeria"
      ],
      "name": "Kevin Nwabueze Ezike"
    },
    {
      "affiliations": [
        "University of Ibadan, Ibadan, Oyo state, Nigeria"
      ],
      "name": "Nwamaka Cynthia Ikeji"
    },
    {
      "affiliations": [
        "University of Ibadan, Ibadan, Oyo state, Nigeria"
      ],
      "name": "Ebenezer Olatunde Farombi"
    }
  ],
  "title": "1268 Age-dependent PI3K/AKT/mTOR signaling dynamics reveal immune microenvironment heterogeneity in Nigerian breast cancer subtypes",
  "uid": "5b68f5d9-980b-52d1-913f-b2e15b62d0ac"
}