Department of General Surgery and Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.
The First Clinical Medical School, Southern Medical University, Guangzhou, China.
Front Immunol. 2022 Mar 25;13:783695. doi: 10.3389/fimmu.2022.783695. eCollection 2022.
Antibodies against programmed death 1 (PD-1) and its ligand, programmed death-ligand 1 (PD-L1) have recently shown promising results in gastric cancer (GC). However, clinicians still lack predictive biomarkers for the efficacy of anti-PD-1 therapy; thus, we investigated the expression of PD-L1 in GC and further assessed its clinical relevance with other clinicopathological features.
We retrospectively collected clinical data on 968 consecutive GC cases from Nanfang Hospital between November 2018 and August 2021. Discrepancy in the combined positive score (CPS) of PD-L1 protein expression between gastric mucosa biopsy and postoperative pathology were investigated. Correlations between CPS and clinicopathological parameters were determined using chi-squared test, multiple logistic aggression analysis, and linear regression analysis.
Among the 968 consecutive GC patients, 199 who did not receive preoperative chemotherapy or immunotherapy were tested for CPS both in gastric mucosa biopsy and postoperative pathology, and the results showed that the CPS of gastric mucosa biopsy was significantly lower than that of postoperative pathology [mean ± SD: 5.5 ± 9.4 vs. 13.3 ± 17.4; M(IQR): 2(5) vs. 5(12), p<0.001)]. 62.3% of patients (579/930) had CPS≥ 1, 49.2% of patients (458/930) had CPS≥5, and 33.3% of patients (310/930) had CPS≥10. Mismatch repair deficiency (dMMR) status was seen in 6.1% of patients (56 of 919). Positive Epstein-Barr virus (EBV) status was detected in 4.4% of patients (38 of 854). The patients with CPS≥1/CPS≥5/CPS≥10 were significantly independently correlated with age, Lauren classification, Ki-67 index, and EBV status. According to linear regression analysis, PD-L1 expression was correlated with age (p<0.001), Ki-67 index (p<0.001), EBV (p<0.001), and Lauren classification (p=0.002).
Our results confirmed that PD-L1 expression has Intratumoral heterogeneity in GC. Furthermore, the variables of age, Ki-67 index, and Lauren classification, which are common and accessible in most hospitals, are worth exploring as potential biomarkers for anti-PD-1 therapy in GC.
程序性死亡 1（PD-1）及其配体程序性死亡配体 1（PD-L1）的抗体最近在胃癌（GC）中显示出了有前景的疗效。然而，临床医生仍然缺乏抗 PD-1 治疗疗效的预测生物标志物；因此，我们研究了 PD-L1 在 GC 中的表达，并进一步评估了其与其他临床病理特征的临床相关性。
我们回顾性地收集了 2018 年 11 月至 2021 年 8 月期间南方医院 968 例连续 GC 病例的临床资料。研究了 PD-L1 蛋白表达的联合阳性评分（CPS）在胃黏膜活检和术后病理之间的差异。采用卡方检验、多因素 logistic 回归分析和线性回归分析来确定 CPS 与临床病理参数之间的相关性。
在 968 例连续 GC 患者中，有 199 例患者在未接受术前化疗或免疫治疗的情况下，同时在胃黏膜活检和术后病理中检测了 CPS，结果显示胃黏膜活检的 CPS 显著低于术后病理[平均值±标准差：5.5±9.4 比 13.3±17.4；中位数（IQR）：2（5）比 5（12），p<0.001]。62.3%（579/930）的患者 CPS≥1，49.2%（458/930）的患者 CPS≥5，33.3%（310/930）的患者 CPS≥10。56 例（6.1%）患者存在错配修复缺陷（dMMR）状态，38 例（4.4%）患者存在 EBV 阳性，检测到 EBV 阳性。CPS≥1/CPS≥5/CPS≥10 的患者与年龄、Lauren 分类、Ki-67 指数和 EBV 状态显著独立相关。根据线性回归分析，PD-L1 表达与年龄（p<0.001）、Ki-67 指数（p<0.001）、EBV（p<0.001）和 Lauren 分类（p=0.002）相关。
我们的结果证实，GC 中 PD-L1 表达存在肿瘤内异质性。此外，年龄、Ki-67 指数和 Lauren 分类等在大多数医院都常见且易于获得的变量，作为 GC 中抗 PD-1 治疗的潜在生物标志物值得进一步探索。
