An In Silico Analysis Identified Members of the Pleckstrin Homology-Like Domain, Family B (PHLDB family) as Potential Prognostic and Predictive Biomarkers of Treatment Response in Breast Cancer Patients

Renan Gomes do Nascimento; Jéssica de Moraes; Danilo de Oliveira Cerqueira; Sandro Jorge Januário

doi:10.4274/ejbh.galenos.2022.2022-3-5

An In Silico Analysis Identified Members of the Pleckstrin Homology-Like Domain, Family B (PHLDB family) as Potential Prognostic and Predictive Biomarkers of Treatment Response in Breast Cancer Patients

Eur J Breast Health. 2022 Jul 1;18(3):235-247. doi: 10.4274/ejbh.galenos.2022.2022-3-5. eCollection 2022 Jul.

Authors

Renan Gomes do Nascimento^{1

2

3}, Jéssica de Moraes^{4

5}, Danilo de Oliveira Cerqueira^{1

3}, Sandro Jorge Januário^{1

6}

Affiliations

¹ Institute of Research and Education in Health of São Paulo (IPESSP), São Paulo-SP, Brazil.
² National Service for Commercial Apprenticeship (SENAC), São Paulo-SP, Brazil.
³ Hospital São Camilo (HSC), São Paulo-SP, Brazil.
⁴ Anhanguera University (UNIAN), Guarulhos-SP, Brazil.
⁵ Secretary of Public Health of Guarulhos (SSPG), Guarulhos-SP, Brazil.
⁶ Cleber Leite College (FCL), Santo André-SP, Brazil.

Abstract

Objective: Breast cancer is the leading cause of morbidity and mortality in women worldwide. This malignant neoplasm can be classified into four clinically relevant subtypes according to the expression of a number of biomarkers. However, these tumors show considerable intratumoral heterogeneity and multidrug resistance. Members of the pleckstrin homology-like domain, family B (PHLDB) play a critical role in the regulation of p53 and AKT signaling pathways, important for cancer and cellular metabolism. The present study was performed to evaluate the expression pattern of PHLDB family members in breast cancer and its potential prognostic and predictive value for therapeutic response using bioinformatics tools.

Materials and methods: This in silico analysis was performed using several online repositories, including UALCAN, GEPIA2, bc-GenExMiner, KM Plotter, PrognoScan and ROC Plotter.

Results: PHLDB family genes were found to be differentially expressed in tumor samples when compared to healthy breast tissue samples. Furthermore, epigenetic regulation may be one of the regulatory mechanisms for the expression of these markers. The PHLDB family of genes proved to be potential markers for predicting the development of lymph node metastasis (p<0.0001) and poor clinical outcome. All members of the PHLDB family were significantly correlated with hormone receptors. High levels of PHLDBs expression were associated with worse overall survival and recurrence-free survival in breast cancer patients. Finally, our data demonstrate that members of the PHLDB family can be promising markers in the stratification of patients who may or may not respond to different available therapies.

Conclusion: Our cumulative results demonstrate that PHLDB family members may be promising biomarkers for predicting prognosis and therapeutic response in breast cancer patients.

Keywords: Breast cancer; PHLDB; biomarkers; in silico analysis.