M. Okano1,2, H. Okayama1, T. Ohtake1, T. Kawaguchi2, L. Yan3, Q. Qi3, S. Liu3, K. Takabe2 1Fukushima Medical University School Of Medicine,Department Of Organ Regulatory Surgery,Fukushima, FUKUSHIMA, Japan 2Roswell Park Cancer Institute,Department Of Surgical Oncology,Buffalo, NY, USA 3Roswell Park Cancer Institute,Department Of Biostatistics & Bioinformatics,Buffalo, NY, USA
Introduction: Annexin A1 (ANXA1) is a calcium-dependent phospholipid-linked protein, involved in anti-inflammatory effects, regulation of cellular differentiation, proliferation and apoptosis. Recently, we reported that ANXA1 is associated with triple-negative breast cancer (TNBC) and its poor prognosis. Inhibition of programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) was reported to suppress progression of TNBC. I In the present study, we evaluated the association between ANXA1 and PD-L1 expression in TNBC.
Methods: The ANXA1 and PD-L1 protein expression in the breast cancer (BrCa) tissues was assessed by IHC staining using an anti-ANXA1 and PD-L1 antibody in 48 TNBC patients and compared the levels with clinicopathological factors. We also validated the result using The Cancer Genome Atlas (TCGA) including RNA-seq data and clinical data.
Results:ANXA1 was positively expressed in 17 of the 48 cases (35.4%). Overall survival was significantly shorter in patients with ANXA1 positive tumors compared with ANXA1 negative tumor (p = 0.0082). No other clinicopathological factor was associated with ANXA1 expression. Utilizing TCGA dataset (n = 1060) for a validation study, high expression of ANXA1 associated with worse overall survival in TNBC patients (n = 111, p = 0.0459), while high expression of ANXA1 demonstrated conversely better overall survival in non-TNBC patients (n = 785, p = 0.0287). There was no survival difference with PD1 expression in our cohort, while high expression of PD-L1 associated with better prognosis in all BrCa patients in TCGA cohort (p = 0.0246). There was no association between ANXA1 and PD-L1 expression in the primary cohort, while high expression levels of ANXA1 demonstrated significant association with high PD-L1 expression in TCGA cohort (p < 0.0001).
Conclusion:These results suggested that ANXA1 is associated with poor prognosis of TNBC .