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

doi:10.19401/j.cnki.1007-3639.2023.05.006

Abstract

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

CLC Number:

R735.2

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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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