Expression of Human Epidermal Growth Factor Receptor-2 Status and Programmed Cell Death Protein-1 Ligand Is Associated With Prognosis in Gastric Cancer.

Huifang Lv,Caiyun Nie,Xiaobing Chen,Jianzheng Wang,Junling Zhang,Keran Sun,Saiqi Wang,Weifeng Xu,Yingjun Liu,Beibei Chen

doi:10.3389/fonc.2020.580045

Huifang Lv, Caiyun Nie + Show 8 more

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https://doi.org/10.3389/fonc.2020.580045

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Abstract

BackgroundPD-L1 and HER-2 are routine biomarkers for gastric cancer (GC). However, little research has been done to investigate the correlation among PD-L1, HER-2, immune microenvironment, and clinical features in GC.MethodsBetween January 2013 and May 2020, a total of 120 GC patients treated with chemotherapy were admitted to Henan Tumor Hospital. We retrospectively identified PD-L1, HER-2 level before chemotherapy and abstracted clinicopathologic features and treatment outcomes. Univariate and multivariate survival analyses were performed to assess the relationship between PD-L1/HER-2 levels and progression-free survival (PFS). The mRNA and tumor microenvironment of 343 patients with GC from The Cancer Genome Atlas (TCGA) were used to explore the underlying mechanism.ResultsWe retrospectively analyzed 120 patients with gastric cancer, including 17 patients with HER-2 positive and 103 patients with HER-2 negative GC. The results showed that the expression of PD-L1 was closely correlated with HER-2 (P = 0.015). Patients with PD-L1/HER-2 positive obtained lower PFS compared to PD-L1/HER-2 negative (mPFS: 6.4 vs. 11.1 months, P = 0.014, mPFS: 5.3 vs. 11.1 months, P = 0.002, respectively), and the PD-L1 negative and HER-2 negative had the best PFS than other groups (P = 0.0008). In a multivariate model, PD-L1 status, HER-2 status, tumor location, and tumor differentiation remained independent prognostic indicators for PFS (P < 0.05). The results of database further analysis showed that the proportion of PD-L1+/CD8A+ in HER-2 negative patients was higher than that in HER-2 positive patients (37.6 vs 20.3%), while PD-L1−/CD8A− was significantly higher in HER-2 positive patients than HER-2 negative patients (57.8 vs. 28.8%). In addition, it showed that not only CD4+T cells, macrophages, and CD8+T cells, but also the associated inflammatory pathways such as IFN-γ/STAT1 were associated with HER-2.ConclusionHER-2 status could predict the efficacy of immune checkpoint inhibitors, and HER-2 status combined with PD-L1 level could predict the prognosis of GC patients.

Highlights

Gastric cancer (GC) is a common malignant tumor in the digestive tract, ranking the second in the global mortality rate of malignant tumors, and more than 50% of new cases are from developing countries [1]
The results showed that the expression of PD-L1 was closely correlated with HER-2 (P = 0.015)
Patients with PD-L1/ HER-2 positive obtained lower progression-free survival (PFS) compared to PD-L1/HER-2 negative, and the PD-L1 negative and HER-2 negative had the best PFS than other groups (P = 0.0008)

Summary

Introduction

Gastric cancer (GC) is a common malignant tumor in the digestive tract, ranking the second in the global mortality rate of malignant tumors, and more than 50% of new cases are from developing countries [1]. The 5-year overall survival rate of metastatic GC is only 5–20% [2]. Some studies have shown that HER-2 positive patients have a high survival rate [10,11,12]. HER-2 positive patients are correlated with serous membrane infiltration, lymph node metastasis, disease stage, distant metastasis, and other clinicopathological characteristics [13, 14]. Other studies have shown no correlation between HER-2 expression and survival [15,16,17]. Little research has been done to investigate the correlation among PD-L1, HER-2, immune microenvironment, and clinical features in GC

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Conclusion