PPFIAI is upregulated in liver metastasis of breast cancer and is a potential poor prognostic indicator of metastatic relapse

Abstract

Although the oncogenic role of PPFIA1 (liprin-αI) in breast cancer has been reported, whether its dysregulation is associated with metastasis risk or survival outcomes in breast cancer patients is not clear. Our primary data showed that PPFIA1 expression was significantly higher in liver metastatic breast tumors than in the primary tumors. Then, we tried to pool previous annotated genomic data to assess the prognostic value of PPFIA1 in distant metastasis-free survival, the risk of metastatic relapse, and metastatic relapse-free survival in breast cancer patients by data mining in two large databases, Kaplan-Meier plotter and bc-GenExMiner 4.0. Results from Kaplan-Meier plotter showed that although high PPFIA1 expression was generally associated with decreased distant metastasis-free survival in estrogen receptor+ patients, subgroup analysis only confirmed significant association in estrogen receptor+/N− (nodal negative) group (median survival, high PPFIAI group vs low PPFIA1 cohort: 191.21 vs 236.22 months; hazard ratio: 2.23, 95% confidence interval: 1.42-3.5, p < 0.001), but not in estrogen receptor+/N+ (nodal positive) group (hazard ratio: 1.63, 95% confidence interval: 0.88-3.03, p = 0.12). In estrogen receptor− patients, there was no association between PPFIA1 expression and distant metastasis-free survival, no matter in Nm (nodal status mixed), N−, or N+ subgroups. In bc-GenExMiner 4.0, Nottingham Prognostic Index-and Adjuvant! Online-adjusted analysis validated the independent prognostic value of PPFIA1 in metastatic risks in estrogen receptor+/N− patients. Based on these findings, we infer that high PPFIA1 expression might be an independent prognostic indicator of increased metastatic relapse risk in patients with estrogen receptor+/N− breast cancer, but not in estrogen receptor+/N+ or estrogen receptor− patients.