Journal Article

Soluble PD-L1 as a diagnostic and prognostic biomarker in resectable gastric cancer patients

Pechianu, Catalin, Necula, Laura, Neagu, Ana-Iulia, Matei, Lilia, Popescu, Irinel, Procop, Alexandru, Sorop, Andrei, Dima, Simona, Dragu, Denisa, Bleotu, Coralia, Diaconu, Carmen C., Herlea, Vlad, Duda, Dan G., Chivu-Economescu, Mihaela, Kitahara, Shuji

2023

Overview

Background In this study, we compared programmed death-ligand 1 (PD-L1) expression in primary tissue samples and its soluble form (sPD-L1) concentration in matched preoperative plasma samples from gastric cancer patients to understand the relationship between tissue and plasma PD-L1 expression and to determine its diagnostic and prognostic value. Methods PD-L1 expression in tissue was assessed by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), and sPD-L1 concentration in plasma was quantified by ELISA. The levels of the CD274 gene, which encodes for PD-L1 protein, were examined as part of bulk tissue RNA-sequencing analyses. Additionally, we evaluated the association between sPD-L1 levels and various laboratory parameters, disease characteristics, and patient outcomes. Results GC patients had significantly higher levels of sPD-L1 in their plasma (71.69 pg/mL) compared to healthy controls (35.34 pg/mL) (p < 0.0001). Moreover, sPD-L1 levels were significantly correlated with tissue PD-L1 protein, CD274 mRNA expression, larger tumor size, advanced tumor stage, and lymph node metastasis. Elevated sPD-L1 levels (> 103.5 ng/mL) were associated with poor overall survival (HR = 2.16, 95%CI 1.15–4.08, p = 0.017). Furthermore, intratumoral neutrophil and dendritic cell levels were directly correlated with plasma sPD-L1 concentration in the GC patients. Conclusions sPD-L1 was readily measurable in GC patients, and its level was associated with GC tissue PD-L1 expression, greater inflammatory cell infiltration, disease progression, and survival. Thus, sPD-L1 may be a useful minimally invasive diagnostic and prognostic biomarker in GC patients.

• Publisher: Springer Nature Singapore,Springer Nature B.V
• Subject: Abdominal Surgery / Apoptosis / B7-H1 Antigen - genetics / Biomarkers / Biomarkers, Tumor - genetics / Cancer Research / Cancer therapies / Dendritic cells / Disease / Enzyme-linked immunosorbent assay / Enzymes / Epstein-Barr virus / Gastric cancer / Gastroenterology / Gene expression / Guanylate cyclase / Humans / Hybridization / Immunohistochemistry / Immunotherapy / L1 protein / Leukocytes (neutrophilic) / Lung cancer / Lymph nodes / Medicine / Medicine & Public Health / Melanoma / Metastases / Metastasis / Oncology / Original Article / Patients / PD-L1 protein / Plasma / Prognosis / Protein expression / Proteins / Stomach Neoplasms - genetics / Stomach Neoplasms - surgery / Surgical Oncology / Tumors