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PD-L1 and miR-34a are Prognostic Factors for Primary Gastric Diffuse Large B-Cell Lymphoma Patients Treated with R-CHOP

Authors Wang J, Shang S, Li J, Deng H, Ouyang L, Xie H, Zhu H, Li Y, Zuo C

Received 31 January 2020

Accepted for publication 10 June 2020

Published 25 June 2020 Volume 2020:12 Pages 4999—5008

DOI https://doi.org/10.2147/CMAR.S247874

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Eileen O'Reilly


Jinfeng Wang,1 Song Shang,1 Junjun Li,1 Hongyu Deng,1 Linda Ouyang,1 Hailong Xie,2 Haizhen Zhu,3 Yajun Li,1 Chaohui Zuo1

1Department of Gastroduodenal and Pancreatic Surgery, Translation Medicine Research Center of Liver Cancer, Laboratory of Digestive Oncology, Affiliated Cancer Hospital of Xiangya Medical School & Hunan Cancer Hospital, Central South University, Changsha, People’s Republic of China; 2Graduates School, Cancer Research Institute, University of South China, Hengyang, People’s Republic of China; 3Institute of Pathogen Biology and Immunology of College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha, People’s Republic of China

Correspondence: Chaohui Zuo
Department of Gastroduodenal and Pancreatic Surgery, Laboratory of Digestive Oncology, Affiliated Tumor Hospital of Xiangya Medical School & Hunan Cancer Hospital, Central South University, Hunan University- Hunan Province Tumor Hospital Joint Center of Liver Cancer Translational Medicine, Changsha, People’s Republic of China
Tel +8673189762140
Email zuochaohui@vip.sina.com
Yajun Li
Department of Gastroduodenal and Pancreatic Surgery, Laboratory of Digestive Oncology, Affiliated Tumor Hospital of Xiangya Medical School & Hunan Cancer Hospital, Central South University, Changsha, People’s Republic of China
Tel +8673189762140
Email liyajun2391@163.com

Introduction: Primary gastric diffuse large B-cell lymphoma (GDLBCL) is a heterogeneous disease in clinicopathological features and prognosis. Programmed death ligand-1 (PD-L1) and microRNA-34a (miR-34a) play crucial roles in GDLBCL progress. The purpose of this research is to explore the clinical significance of PD-L1 and miR-34a expression in GDLBCL.
Patients and Methods: The expressions of PD-L1 and miR-34a were examined by IHC and qRT-PCR in 109 patients who were diagnosed with GDLBCL and were treated with rituximab plus cyclophosphamide, doxorubicin, prednisone vincristine and prednisone chemotherapy (R-CHOP) from January 2010 to December 2018.
Results: PD-L1 level was significantly higher in tumor tissues than adjacent non-tumor tissues (60.5%, P< 0.001), while the miR-34a level was just reversed (50.5%, P< 0.001), which was negatively correlated (r=− 0.524, P< 0.001). Notably, PD-L1-positive and miR-34a-negative expressions were significantly correlated with the advanced Lugano stage of IIE-IV stage (P< 0.001 and P< 0.01), elevated serumal LDH levels (P< 0.001 and P< 0.05), B symptoms present (P< 0.001 and P< 0.001), non-GCB subtype (P< 0.001 and P< 0.001) and negative Bcl-2 expression (P< 0.05 and P< 0.001). PD-L1 high and miR-34a low expression groups had more patients with IPI scores of 2 or greater (P< 0.001 and P< 0.05) and poor R-IPI (P< 0.01 and P< 0.01). The complete response rate was upregulated in patients with negative PD-L1 and positive miR-34a expression after R-CHOP treatment.
Discussion: PD-L1 expression and miR-34a expression were significantly associated with clinicopathological characteristics and survival prognosis; they may serve as novel prognostic markers in GDLBCL patients who were treated with R-CHOP. Immunotherapies targeting PD-L1 and miR-34a pathway may have therapeutic potential in GDLBCL.

Keywords: GDLBCL, R-CHOP, PD-L1, miR-34a, tumor immunotherapy

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