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PICALM as a Novel Prognostic Biomarker and Its Correlation with Immune Infiltration in Breast Cancer

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Abstract

PICALM (phosphatidylinositol-binding clathrin assembly protein) mutations have been linked to a number of human disorders, including leukemia, Alzheimer’s disease, and Parkinson’s disease. Nevertheless, the effect of PICALM on cancer, particularly on prognosis and immune infiltration in individuals with BRCA, is unknown. We obtained the data of breast cancer patients from The Cancer Genome Atlas (TCGA) database, and analyzed the expression of PICALM in breast cancer, its impact on survival’ and its role in tumor immune invasion. Finally, in vitro cellular experiments were performed to validate the results. Research has found that PICALM expression was shown to be downregulated in BRCA and to be substantially linked with clinical stage, histological type, PAM50, and age. PICALM downregulation was linked to a lower overall survival (OS) and disease-specific survival (DSS) in BRCA patients. A multivariate Cox analysis revealed that PICALM is an independent predictor of OS. The enriched pathways revealed by functional enrichment analysis included oxidative phosphorylation, angiogenesis, the TGF signaling pathway, and the IL-6/JAK/STAT3 signaling system. Furthermore, the amount of immune cell infiltration by B cells, eosinophils, mast cells, neutrophils, and T cells was positively linked with PICALM expression. Finally, we experimentally verified that low expression of PICALM can reduce proliferation, migration, and invasion in tumor cells. This evidence shows that PICALM expression impacts prognosis, immune infiltration, and pathway expression in breast cancer patients, and it might be a potential predictive biomarker for the disease.

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Data Availability

The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank the TCGA database for sharing a large amount of data and the convenience provided by several online database tools. At the same time, thank you to Baidu Translate and DeepL for providing free translation and polishing.

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Authors and Affiliations

  1. The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhuxi Road, Hexi District, Tianjin, 300060, China

    Naer A, Yue Yu & Xuchen Cao

  2. Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China

    Naer A & Xuchen Cao

  3. Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, China

    Naer A & Xuchen Cao

  4. Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, 300060, China

    Naer A & Xuchen Cao

  5. Department of Breast Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, 570102, China

    Pengfei Lyu

  6. Department of Thyroid and Breast Surgery, Shenzhen Bao’an District Songgang People’s Hospital, No. 2 Shajiang Road, Shenzhen City, 518105, Guangdong Province, China

    Meiling Liu, Shaohua Cheng, Meiyan Chen & Yunhong Liu

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All authors contributed to the study’s conception and design. All authors read and approved the final manuscript. All authors commented on previous versions of the manuscript. All authors agree to become authors of the manuscript.

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A, N., Lyu, P., Yu, Y. et al. PICALM as a Novel Prognostic Biomarker and Its Correlation with Immune Infiltration in Breast Cancer. Appl Biochem Biotechnol (2024). https://doi.org/10.1007/s12010-023-04840-z

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