To analyze the clinical value of Eph receptor A (EPHA) 5 mutation in predicting the prognosis of lung adenocarcinoma (LUAD) treated with immune checkpoint inhibitors (ICI).

The mutation genes that may be associated with ICI response in LUAD patients were analyzed by bioinformatics in the genomics of drug sensitivity in cancer (GDSC)-LUAD dataset and the cancer genome atlas (TCGA)-LUAD dataset. A clinical cohort of 96 LUAD patients treated with pembrolizumab in our hospital from January 2020 to January 2021 was retrospectively enrolled. The patients′paraffin-embedded tissue tumor specimens and matched blood samples were collected for next-generation sequencing. According to the results, the patients were divided into EPHA5-WT subgroup 66 cases and EPHA5-MT 30 cases subgroup. The objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) were recorded.

Bioinformatics analysis showed that LUAD patients with EPHA5-MT could benefit from ICI treatment. The results of clinical cohort analysis showed that the tumor mutation burden value of LUAD patients in the EPHA5-MT subgroup was significantly higher than that in the EPHA5-WT subgroup [27.34(19.98, 53.24) mut/Mb vs. 13.70(10.77, 17.75) mut/Mb, P<0.001]. There was no significant difference in ORR between EPHA5-WT subgroup and EPHA5-MT subgroup (22.73% vs. 33.33%, P=0.272), but the DCR of EPHA5-MT subgroup was higher than that of EPHA5-WT subgroup (86.67% vs. 62.12%, P=0.029). Thirty-six patients (54.55%) in the EPHA5-WT subgroup and 8 patients (26.67%) in the EPHA5-MT subgroup experienced disease progression. Univariate and multivariate COX regression analysis showed that EPHA5-WT was an independent risk factor for LUAD disease progression compared with EPHA5-MT. Kaplan-Meier survival curve showed that the PFS of EPHA5-MT group was longer than that of EPHA5-WT group [14.53(5.71~26.23) months vs. 7.89(0.59~30.67)months, P<0.001].

EPHA5-MT is a potential biomarker for the prognosis of LUAD patients treated with ICI.