Effect of Primary Systemic Therapy on PD-1, PD-L1, and PD-L2 mRNA Expression in Advanced Breast Cancer

Karsono, Ramadhan and Azhar, Muhammad Al and Pratiwi, Yulia and Saputra, Fahreza and Nadliroh, Siti and Aryandono, Teguh (2021) Effect of Primary Systemic Therapy on PD-1, PD-L1, and PD-L2 mRNA Expression in Advanced Breast Cancer. Asian Pacific Journal of Cancer Prevention, 22 (7). 2069 – 2077. ISSN 15137368

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Abstract

Objective: The association between PD-1, PD-L1, and PD-L2 expression and prognosis has been extensively studied in various cancers but remained controversial in breast cancer. Besides, little is known about the prognostic value of PD-1, PD-L1, and PD-L2 upregulation or downregulation following systemic therapy (chemotherapy and hormonal therapy) in breast cancer. Therefore, we aim to investigate the change of PD-1, PD-L1, and PD-L2 expression in mRNA level after primary systemic therapy in breast cancer patients and its clinical implications. Methods: Expression of PD-1, PD-L1, and PD-L2 mRNA were measured before-after chemotherapy and hormonal therapy with real-time PCR in 80 advanced breast cancer patients. The correlation between alteration of PD-1, PD-L1, and PD-L2 expression and clinicopathological characteristics as well as overall survival was also statistically analyzed. Results: Chemotherapy and hormonal therapy altered PD-1, PD-L1, and PD-L2 expression in breast cancer with most patients have an increase expression. As much as 57.1, 62.9 and 60 patients have an increase PD-1, PD-L1, and PD-L2 expression after chemotherapy, while 60, 60, and 64 patients have an increase PD-1, PD-L1, and PD-L2 expression after hormonal therapy. Alteration of PD-1, PD-L1, and PD-L2 expression was not correlated with all clinicopathological characteristics. Increase in PD-1, PD-L1, and PD-L2 expression was significantly associated with better OS (p=0.031, p=0.019, and p=0.019 for PD-1, PD-L1, and PD-L2, respectively), which remained significant in multivariate analysis including age, stage, primary systemic therapy, histology grade, subtype and primary tumor histology (HR PD-1 0.5 (95 CI 0.28-0.88) p=0.031; HR PD-L1 0.43 (95 CI 0.24-0.8) p=0.019; HR PD-L2 (95 CI 0.24-0.87) p=0.019). Conclusion: Expression of PD-1, PD-L1, and PD-L2 in breast cancer patients is mostly enhanced after chemotherapy and hormonal therapy, and the enhancement is associated with good OS. This result revealed the potential of measuring PD-1, PD-L1, and PD-L2 mRNA expression in predicting clinical outcome. © 2021. All rights reserved.

Item Type: Article
Additional Information: Cited by: 2; All Open Access, Gold Open Access, Green Open Access
Uncontrolled Keywords: Adult; B7-H1 Antigen; Breast Neoplasms; Female; Humans; Middle Aged; Prognosis; Programmed Cell Death 1 Ligand 2 Protein; Programmed Cell Death 1 Receptor; RNA, Messenger; CD274 protein, human; messenger RNA; programmed death 1 ligand 1; programmed death 1 ligand 2; programmed death 1 receptor; adult; breast tumor; female; human; metabolism; middle aged; pathology; prognosis
Subjects: R Medicine > RB Biomedical Sciences
Divisions: Faculty of Medicine, Public Health and Nursing > Biomedical Sciences
Depositing User: Sri JUNANDI
Date Deposited: 27 Sep 2024 02:29
Last Modified: 27 Sep 2024 02:29
URI: https://ir.lib.ugm.ac.id/id/eprint/4584

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