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

doi:10.19401/j.cnki.1007-3639.2023.05.006

中国癌症杂志 ›› 2023, Vol. 33 ›› Issue (5): 460-468.doi: 10.19401/j.cnki.1007-3639.2023.05.006

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¹^,²(), 陈志强³, 董润雨¹, 王智雄¹, 蔡娟²^,⁴()

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（ORCID: 0000-0001-7996-2525），博士，副主任医师。
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)

The value of combined detection of LDHA and PD-L1 in predicting the efficacy and prognosis of advanced gastric cancer patients treated with PD-1 inhibitor

ZUO Xueliang¹^,²(), CHEN Zhiqiang³, DONG Runyu¹, WANG Zhixiong¹, CAI Juan²^,⁴()

1. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wuhu 241001, Anhui Province, China
2. Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wuhu 241001, Anhui Province, China
3. Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
4. Department of Oncology, The First Affiliated Hospital, Yijishan Hospital of Wannan Medical College, Wuhu 241001, Anhui Province, China

Received:2022-10-26 Revised:2023-03-02 Published:2023-05-30 Online:2023-06-16
Contact: CAI Juan

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

中图分类号:

R735.2

左学良, 陈志强, 董润雨, 王智雄, 蔡娟. 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[J]. 中国癌症杂志, 2023, 33(5): 460-468.

ZUO Xueliang, CHEN Zhiqiang, DONG Runyu, WANG Zhixiong, CAI Juan. The value of combined detection of LDHA and PD-L1 in predicting the efficacy and prognosis of advanced gastric cancer patients treated with PD-1 inhibitor[J]. China Oncology, 2023, 33(5): 460-468.

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参考文献 27

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Characteristic	LDHA low expression	LDHA high expression	χ² value	P value
Gender			0.021	0.886
Female	6	4
Male	23	17
Age/year			0.618	0.432
<60	8	8
≥60	21	13
Tumor location			0.019	0.890
Down	16	12
Upper/middle	13	9
ECOG performance score			0.069	0.793
0-1	19	13
≥2	10	8
HER2 expression			0.114	0.735
Negative	27	19
Positive	2	2
Metastasis sites			0.618	0.432
≤2	21	13
>2	8	8
PD-L1 CPS			1.439	0.230
≥5	10	4
<5	19	17
PD-1 inhibitor response
PD	5	15	16.811	<0.001
SD	7	4
PR	17	2

Characteristic	Responder	Non-responder	χ² value	P value
Gender			0.764	0.382
Female	5	5
Male	14	26
Age/year			3.701	0.054
<60	3	13
≥60	16	18
Tumor location			2.401	0.121
Down	8	20
Upper/middle	11	11
ECOG performance score			0.496	0.481
0-1	11	21
≥2	8	10
HER2 expression			0.312	0.577
Negative	18	28
Positive	1	3
Metastasis sites			3.701	0.054
≤2	16	18
>2	3	13
Immunotherapy line			7.371	0.007
First-line	7	2
Second-line and above	12	29
PD-L1 CPS			13.585	<0.001
≥5	11	3
<5	8	28
LDHA expression			12.462	<0.001
Low	17	12
High	2	19

Characteristic	OR	95% CI	P value
Immunotherapy line (second and above)	19.757	0.945-413.003	0.054
PD-L1 CPS<5	24.180	2.049-285.278	0.011
LDHA high expression	44.987	2.916-693.960	0.006

Characteristic	OS		PFS
Characteristic	Log-rank	P value	Log-rank	P value
Gender (male vs female)	0.085	0.770	0.060	0.806
Age (≥60 years vs <60 years)	1.914	0.167	3.063	0.080
Tumor location (upper/middle vs down)	1.034	0.309	0.847	0.357
ECOG performance score (≥2 vs <2)	1.302	0.254	0.894	0.344
HER2 expression (positive vs negative)	0.173	0.677	0.079	0.778
Metastasis sites (>2 vs ≤2)	5.195	0.023	5.744	0.017
Immunotherapy line (first vs second and above)	1.994	0.158	2.597	0.107
PD-L1 CPS (<5 vs ≥5)	9.334	0.002	9.004	0.003
LDHA expression (high vs low)	7.265	0.007	14.913	<0.001

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

The value of combined detection of LDHA and PD-L1 in predicting the efficacy and prognosis of advanced gastric cancer patients treated with PD-1 inhibitor

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