Attenuated ZHX3 expression serves as a potential biomarker that predicts poor clinical outcomes in breast cancer patients

Background: The ZHX family has recently been in the spotlight as an integrator and an indispensable node in carcinogenesis, whose expression is frequently dysregulated in multiple cancers. The current study provides a novel investigation of the expression profiles of ZHX factors in breast cancer. Materials and methods: The mRNA levels of ZHXs and follow-up periods in breast cancer patients were mined through the Oncomine, Cancer Cell Line Encyclopedia, bc-GenExMiner, cBioPortal and Kaplan-Meier plotter databases. In addition, ZHX3 protein expression was examined in 98 primary tumor samples by immunohistochemistry to investigate its association with clinicopathological parameters and patient outcomes. Results: We found that the transcriptional levels of ZHX1, ZHX2 and ZHX3 were not significantly altered in tumor tissues compared with those in nontumor tissues. ZHX2 and ZHX3 mRNA levels were observed to be positively correlated with estrogen receptor and progesterone receptor expression, while ZHX2 mRNA levels were negatively associated with HER2 expression. Survival analyses revealed that high mRNA levels of ZHX2 and ZHX3 correlated with better overall survival in patients with breast cancer. Immunohistochemical analysis revealed that patients with decreased ZHX3 protein levels had poorer outcomes. Multivariate analysis exhibited that ZHX3 expression may serve as an independent high-risk prognostic predictor. Conclusion: Dysregulated expression of ZHXs may be involved in the progression of breast cancer and could serve as a novel biomarker and potential target for breast cancer.