联合检测LDHA和PD-L1在晚期胃癌PD-1抑制剂疗效预测及预后评估中的价值

左学良, 陈志强, 董润雨, 王智雄, 蔡娟

  1. 1.皖南医学院第一附属医院（弋矶山医院）胃肠外科，安徽 芜湖 241001
    2.重大疾病非编码RNA转化研究安徽普通高校重点实验室，安徽 芜湖 241001
    3.南京医科大学第一附属医院肝胆中心，江苏 南京 210029
    4.皖南医学院第一附属医院（弋矶山医院）肿瘤内科，安徽 芜湖 241001
  • 收稿日期:2022-10-26 修回日期:2023-03-02 出版日期:2023-05-30 发布日期:2023-06-16
  • 通信作者: 蔡娟
  • 作者简介:左学良（ORCID: 0000-0001-5204-2585），博士，副主任医师。
  • 基金资助:
    国家自然科学基金(82103293);安徽省高校优秀青年人才支持计划(gxyq2021257);芜湖市科技计划(2022jc52)

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摘要/Abstract

摘要：

背景与目的：胃癌对程序性死亡[蛋白]-1（programmed death-1，PD-1）抑制剂的应答率较低，建立有用的疗效预测方法筛选胃癌PD-1抑制剂治疗优势人群对改善患者预后有重要意义。本研究旨在探讨联合检测乳酸脱氢酶A（lactate dehydrogenase，LDHA）和程序性死亡[蛋白]配体-1（programmed death ligand-1，PD-L1）表达对接受PD-1抑制剂治疗胃癌患者的疗效预测和预后评估价值。方法：回顾性分析皖南医学院第一附属医院2020年1月—2022年3月接受PD-1抑制剂治疗的50例晚期胃癌患者的临床病理学资料，采用多因素logistic回归分析影响胃癌PD-1抑制剂疗效的独立危险因素，利用受试者工作特征（receiver operating characteristic，ROC）曲线分析联合检测LDHA和PD-L1对胃癌PD-1抑制剂疗效的预测价值，应用Kaplan-Meier法对患者进行生存分析。结果：LDHA低表达组和高表达组胃癌患者的客观缓解率（objective response rate，ORR）分别为59%和10%，疾病控制率（disease control rate，DCR）分别为83%和29%，差异有统计学意义（P<0.001）。多因素logistic回归分析结果显示，PD-L1阳性联合分数（combined positive score，CPS）<5、LDHA高表达是胃癌PD-1抑制剂疗效不佳的独立危险因素（P<0.05）。ROC曲线分析结果提示LDHA联合PD-L1具有较好的胃癌PD-1抑制剂疗效预测价值[曲线下面积（area under curve，AUC）为0.951]。Kaplan-Meier生存分析显示，LDHA低表达合并PD-L1 CPS≥5的胃癌患者在接受PD-1抑制剂治疗后具有更长的总生存期（overall survival，OS，P=0.003）和无进展生存期（progression-free survival，PFS，P<0.001）。结论：LDHA低表达、PD-L1 CPS≥5与胃癌PD-1抑制剂的疗效呈正相关，LDHA低表达合并PD-L1 CPS≥5的胃癌患者接受PD-1抑制剂治疗可显著延长OS和PFS，联合检测LDHA和PD-L1对晚期胃癌患者PD-1抑制剂的疗效预测和预后评估有一定的临床应用价值。

关键词: 胃肿瘤, 免疫检查点抑制剂, 免疫治疗, 疗效, 预后

Abstract:

Background and purpose: The response rate of gastric cancer patients to programmed death-1 (PD-1) inhibitor is relatively low. Establishing a useful efficacy prediction method to screen the superior gastric cancer patients receiving anti-PD-1 therapy could improve the prognosis of patients. This study aimed to explore the value of combined detection of lactate dehydrogenase (LDHA) and programmed death ligand-1 (PD-L1) expressions in predicting the efficacy and prognosis of gastric cancer patients treated with PD-1 inhibitor. Methods: The clinicopathological data of 50 advanced gastric cancer patients treated with PD-1 inhibitor in The First Affiliated Hospital of Wannan Medical College from January 2020 to March 2022 were retrospectively analyzed. The independent risk factors affecting the efficacy of PD-1 inhibitor were analyzed by multivariate logistic regression. The value of combined detection of LDHA and PD-L1 in predicting the efficacy of PD-1 inhibitors in gastric cancer was analyzed by receiver operating characteristic (ROC) curve analysis. Gastric cancer patient survival was analyzed by Kaplan-Meier method. Results: The objective response rate (ORR) of gastric cancer patients receiving PD-1 inhibitor therapy in LDHA low and high expression groups were 59% and 10%, respectively. The disease control rate (DCR) in LDHA low and high expression groups were 83% and 29%, respectively. The difference was statistically significant (P<0.001). Multivariate logistic regression analysis showed that PD-L1 combined positive score (CPS)<5 and LDHA high expression were independent risk factors affecting the efficacy of PD-1 inhibitor in gastric cancer (P<0.05). ROC curve analysis showed that combined detection of LDHA and PD-L1 had good predictive value for the efficacy of PD-1 inhibitor in gastric cancer [area under curve (AUC) was 0.951]. Kaplan-Meier survival analysis showed that gastric cancer patients with low LDHA expression and PD-L1 CPS≥5 had longer overall survival (OS, P=0.003) and progression-free survival (PFS, P<0.001) after receiving PD-1 inhibitor therapy. Conclusion: Low LDHA expression and PD-L1 CPS≥5 were positively correlated with the efficacy of PD-1 inhibitor in gastric cancer. Gastric cancer patients with low LDHA expression and PD-L1 CPS≥5 significantly had prolonged OS and PFS after receiving PD-1 therapy. Therefore, the combined detection of LDHA and PD-L1 expressions has good value in predicting the efficacy and evaluating prognosis of advanced gastric cancer patients treated with PD-1 inhibitor.

Key words: Stomach neoplasms, Immune checkpoint inhibitors, Immunotherapy, Efficacy, Prognosis

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