High PGAP3 expression is associated with lymph node metastasis and low CD8+T cell in patients with HER2+ breast cancer

Pathol Res Pract. 2023 Nov:251:154890. doi: 10.1016/j.prp.2023.154890. Epub 2023 Oct 13.

Abstract

Background: Breast cancer (BC) stands as the most prevalent malignancy among women and ranks as the second most frequently diagnosed cancer globally among newly identified cases. Post-GPI attachment to proteins factor 3(PGAP3)was reported to involve in lipid remodeling. However, its specific role in breast cancer remains inadequately elucidated. Consequently, the principal objective of this study was to investigate the clinical significance of PGAP3 in breast cancer.

Methods: We conducted an extensive analysis using both public databases and our own sample cohort to assess the role of PGAP3 in breast cancer. Immunohistochemistry was employed to assess PGAP3 expression, immune markers, and the co-expression of PGAP3 with key susceptibility genes. Data analysis was performed using the R programming language.

Results: Our findings revealed that PGAP3 is significantly overexpressed in breast cancer, particularly in human epidermal growth factor 2 positive (HER2 +) breast cancer cases (p < 0.001). Co-expression analyses demonstrated a significant correlation between PGAP3 and susceptibility genes associated with breast cancer, including BRCA1, BRCA2, PALB2, ATM, CHEK2, RAD51C, and RAD51D (p < 0.05). Logistic regression analysis identified PGAP3 as a significant predictor of estrogen receptor (ER), progesterone receptor (PR), HER2, and lymph node metastasis status (p < 0.01). Furthermore, higher PGAP3 expression was associated with decreased infiltration of CD8 + T cells in breast cancer samples.

Conclusion: Our study sheds light on the clinical significance of PGAP3 in breast cancer. PGAP3 is not only overexpressed in breast cancer but also correlates with key susceptibility genes, lymph node metastasis, and CD8 + T cell infiltration. These findings provide valuable insights into the potential role of PGAP3 as a biomarker in breast cancer and may contribute to our understanding of the disease's pathogenesis.

Keywords: Breast cancer; PGAP3; Pathology; Prognosis.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms* / pathology
  • CD8-Positive T-Lymphocytes
  • Carboxylic Ester Hydrolases
  • Female
  • Humans
  • Lymphatic Metastasis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Cell Surface
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone

Substances

  • Receptor, ErbB-2
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Biomarkers, Tumor
  • PGAP3 protein, human
  • Carboxylic Ester Hydrolases
  • Receptors, Cell Surface