The prognostic significance of protein tyrosine phosphatase 4A2 in breast cancer

Abstract

Duanzheng Zhao,1 Libin Guo,2,* Henrique Neves,3,* Hiu-Fung Yuen,4 Shu-Dong Zhang,5 Cian M McCrudden,6 Qing Wen,5 Jin Zhang,2 Qi Zeng,4 Hang Fai Kwok,3,5,6 Yao Lin2 1College of Continuing Education, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, People’s Republic of China; 2College of Life Sciences, Fujian Normal University, Fuzhou, Fujian, People’s Republic of China; 3Faculty of Health Sciences, University of Macau, Avenida de Universidade, Taipa, Macau Special Administrative Region, People’s Republic of China; 4Institute of Molecular and Cell Biology, Biopolis Drive, Proteos, Singapore; 5Center for Cancer Research and Cell Biology, 6School of Pharmacy, Queen’s University of Belfast, Belfast, UK *These authors have contributed equally to this work Abstract: Although PTP4A3 has been shown to be a very important factor in promoting cancer progression, the role of its close family member PTP4A2 is still largely unknown. Recent reports have shown contradicting results on the role of PTP4A2 in breast cancer progression. Considering this, we aimed to investigate the prognostic value of PTP4A2 in five independent breast cancer data sets (minimum 198 patients per cohort, totaling 1,124 patients) in the Gene Expression Omnibus Database. We found that high expression of PTP4A2 was a favorable prognostic marker in all five independent breast cancer data sets, as well as in the combined cohort, with a hazard ratio of 0.68 (95% confidence interval =0.56–0.83; P<0.001). Low PTP4A2 expression was associated with estrogen receptor-negative tumors and tumors with higher histological grading; furthermore, low expression was inversely correlated with the expression of genes involved in proliferation, including MKI67 and the MCM gene family encoding the minichromosome maintenance proteins. These findings suggest that PTP4A2 may play a role in breast cancer progression by dysregulating cell proliferation. PTP4A2 expression was positively correlated with ESR1, the gene encoding estrogen receptor-alpha, and inversely correlated with EGFR expression, suggesting that PTP4A2 may be involved in these two important oncogenic pathways. Together, our results suggest that expression of PTP4A2 is a favorable prognostic marker in breast cancer. Keywords: breast cancer, PTP4A2, survival, prognostic marker, overexpression, minichromosome maintenance proteins