A panel containing PD-1, IL-2R alpha, IL-10, and CA15-3 as a biomarker to discriminate breast cancer from benign breast disease

作者：Liu, Chao; Sun, Bing; Xu, Bin; Meng, Xiangying; Li, Lan; Cong, Yang; Liu, Jiannan; Wang, Qian; Xuan, Liang; Song, Qibin^*; Wu, Shikai^*

来源：Cancer Management and Research, 2018, 10(4_suppl_2): 1749-1761.

DOI：10.2147/CMAR.S160452

• breast cancer
• immune checkpoint
• PD-1
• CTLA-4
• IL-2R alpha
• diagnosis
• biomarker

Introduction: Programmed cell death protein 1 (PD-1), an immune checkpoint molecule, has recently been recognized as a predictive and prognostic biomarker in several malignant tumors, but its diagnostic value remains largely unknown. We aimed to investigate the differential diagnostic efficiency of PD-1 and other immune molecules and propose a panel of immune molecules combined with cancer antigen 15-3 (CA15-3) to distinguish breast cancer (BC) from benign breast disease (BBD).
Patients and methods: Ninety-one eligible BC patients and 31 BBD patients were enrolled. Pretreatment peripheral blood was collected and tested for mRNA expression of PD-1, cytotoxic T lymphocyte antigen 4, forkhead box P3, transforming growth factor beta, interleukin-10 (IL-10), IL-2 receptor alpha (IL-2R alpha), and cluster of differentiation 28 by quantitative reverse transcription PCR.
Results: The diagnostic areas under curve (AUCs) of PD-1, IL-2R alpha, and IL-10 for BC-BBD discrimination were 0.764, 0.758, and 0.743, respectively. The diagnostic efficiencies of these three parameters in distinguishing early-stage or advanced BC from BBD were consistent with a role in BC-BBD discrimination. A panel of PD-1 + IL-10 + IL-2R alpha + CA15-3 showed the highest AUC (0.862), with a sensitivity of 0.933 and a specificity of 0.724, for BC-BBD discrimination. In addition, for early-stage BC discrimination, this panel also had the highest AUC (0.811), with a sensitivity of 0.933 and a specificity of 0.614, while for advanced BC discrimination, a panel of PD-1 + IL-10 + CA15-3 exhibited the highest AUC (0.896), with a sensitivity of 0.933 and a specificity of 0.783.
Conclusion: These data indicate that the panel containing PD-1, IL-2R alpha, IL-10, and CA15-3 can effectively discriminate BC from BBD with a high efficiency. After further confirmation, it could be used to complement conventional imaging modalities, especially in discriminating early-stage BC from BBD.

• 出版日期2018
• 单位中国人民解放军军事医学科学院; 武汉大学