The Prognostic Role of HuR Varies Between Different Subtypes of Breast Cancer Patients: Data Mining and Retrospective Analysis

Abstract

Objective

Human-antigen R (HuR) is an RNA-binding protein, which regulates the expression of several oncogenes and tumor suppressor genes through post-transcriptional mechanisms. But the role of HuR in breast cancer remains controversial. The aim of this study was to verify the association between cytoplasmic HuR level and prognosis of breast cancer patients.

Methods

Data mining from the Human Protein Atlas (HPA) and Kaplan–Meier Plotter (KMP) databases was performed. Then, 394 patients with stage I–III primary breast cancer were enrolled between January 2005 and December 2016. We investigated the association between cytoplasmic HuR level and clinicopathological characteristics or survival of these patients. Immunohistochemical analysis was performed to determine HuR expression level. SPSS 21.0 statistical software was used for analysis.

Results

In the HPA and KMP datasets, HuR protein and mRNA expression level were not significantly associated with overall survival of all breast cancer patients enrolled. Results from our 394 patients indicated that higher expression level of cytoplasmic HuR was associated with larger tumor size, lymph node positive, ER negative and triple-negative subtype. For all patients enrolled, the results indicated that compared with HuR negative patients, the DFS (disease-free survival) of HuR 1+ was longer (60.5% vs 78.8, P=0.053, HR=0.616, 95% CI: 0.378–1.005), the P value was borderline. In the triple-negative breast cancer (TNBC) subgroup, HuR positive patients had significantly longer DFS than HuR negative patients (65.5% vs 30.8%, P=0.001, HR=0.345, 95% CI: 0.180–0.658). In the HR+HER2– subgroup, HuR low (0~1+) patients had significantly longer OS than HuR high (2+~3+) patients (97.0% vs 89.5%, P=0.033, HR=2.482, 95% CI: 1.074–5.736).

Conclusion

In conclusion, our results revealed that higher expression level of HuR was related to aggressive biological characteristics which supported the findings from previous researches. In the HR+HER2– subgroup, lower HuR expression level patients had better survival time, while in the TNBC subgroup we got the opposite results. Our work indicated that HuR might play different roles in different breast cancer subtypes.

Keywords:

• human antigen R
• breast cancer
• immunohistochemistry
• clinicopathological parameters
• prognosis

Ethical Standards

This investigation was approved by the Institutional Review Board of the Chinese Academy of Medical Sciences Cancer Hospital and the First Affiliated Hospital of Nanchang University. It was conducted according to the ethical standards of the Declaration of Helsinki and following the national and international guidelines. All patients have consented to their tumor tissue and clinical information being used in this study. We collected clinical and pathological data. Patients were followed until December 2021 to collect data on recurrence and death.

Acknowledgment

This study was funded by the Science and technology plan from Health Commission of Jiangxi Province in China (No. SKJP220203930) and Science and technology plan from Administration of Traditional Chinese Medicine of Jiangxi Province in China (No. SZYYB20205193).

Disclosure

The authors declare no competing interests in this work.