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Review
. 2025 Jun 3;15(11):1420.
doi: 10.3390/diagnostics15111420.

PAX Family, Master Regulator in Cancer

Erica Giacobbi  1 , Maria Paola Scioli  1 , Francesca Servadei  1 , Valeria Palumbo  1 , Rita Bonfiglio  1 , Pierluigi Bove  2 , Alessandro Mauriello  1 , Manuel Scimeca  1
Affiliations
Review

PAX Family, Master Regulator in Cancer

Erica Giacobbi et al. Diagnostics (Basel). .

Abstract

PAX genes, known as master regulators, encode paired box (PAX) proteins that govern key processes in organ development and are widely expressed in normal tissues. Notably, PAX proteins also play a pivotal role in both promoting and suppressing tumorigenesis. They influence essential cellular functions such as survival, proliferation, fate determination, differentiation, invasion, metastasis, and the formation of oncogenic fusion proteins. In this review, we summarize the current understanding of these transcription factors. First, we provide a brief overview of their molecular structure, which underlies their classification into four subgroups. Then, we examine the expression patterns of each PAX gene across organ systems and explore their biological roles in the most relevant malignant neoplasms affecting human health. Additionally, we highlight their diagnostic, prognostic, and predictive significance in the context of cancer.

Keywords: EMT; PAX family; cancer; cell death; therapy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Bioinformatic analysis of PAX5 and PAX5 expression in Breast Carcinomas. (A) The expression of PAX5 does not influence overall survival in breast cancer patients. (B) A significant increase in PAX5 expression is observed in primary tumors and metastatic lesions compared to normal tissues. (C) Overall survival of breast cancer patients based on the expression of PAX6. (D) A significant increase in PAX6 expression is observed in primary tumors compared to normal tissues. Gene expression data from the TCGA Breast Cancer (BRCA) cohort are available through the UCSC Xena platform (https://xena.ucsc.edu/compare-tissue/), accessed on 28 March 2025. ** p < 0.01, **** p < 0.0001.
Figure 2
Figure 2
Bioinformatic analysis of PAX8 expression in a thyroid carcinoma. (A) The expression of PAX8 does not influence overall survival in thyroid cancer patients. (B) A significant decrease in PAX8 expression is observed in primary tumors and metastatic lesions compared to normal tissues. Gene expression data from the TCGA Thyroid Cancer (THCA) cohort are available through the UCSC Xena platform (https://xena.ucsc.edu/compare-tissue/), accessed on 28 March 2025. *** p < 0.001; **** p < 0.0001.
Figure 3
Figure 3
Bioinformatic and single cell transcriptomic analysis of PAX8 expression in clear cell carcinomas. (A) Patients with clear cell carcinoma exhibit reduced overall survival compared to those with lower expression levels. (B) A significant decrease in PAX8 expression is observed in primary tumors as compared to normal tissues. (C) Mutations in PAX8-AS1 are significantly associated with reduced overall survival, as patients harboring these mutations exhibit poorer prognoses. (D) Single-cell transcriptomic analysis reveals high expression of PAX8 in several cell types, including cancer cells. (E) Cell-type-specific analysis shows higher PAX8 expression in malignant cells compared to inflammatory cells. Gene expression data from the TCGA Kidney Clear Cell Carcinoma (KIRK) cohort are available through the UCSC Xena platform (https://xena.ucsc.edu/compare-tissue/), accessed on 28 March 2025 (Panel A–C). Single-cell transcriptomic data for PAX8 are available through the TISCH portal (http://tisch.comp-genomics.org/), accessed on 28 March 2025. *** p < 0.001.
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