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