ArticleCancer medicine2022
ENPEP as a potential predictor of immune checkpoint inhibitor efficacy.
Article in Cancer medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- Potential therapeutic targets for colorectal cancer and its subsites: evidence from the proteome-wide Mendelian randomization analyses.Translational cancer research · 2025Article
- Unveiling the role of TGF-β signaling pathway in breast cancer prognosis and immunotherapy.Frontiers in oncology · 2024Article
- Article
- Long non-coding RNA NCK1-AS1 functions as a ceRNA to regulate cell viability and invasion in esophageal squamous cell carcinoma via microRNA-133b/ENPEP axis.Cell cycle (Georgetown, Tex.) · 2023Article
- A novel immunogenic cell death-related subtype classification and risk signature for predicting prognosis and immunotherapy efficacy in gastric cancer.Frontiers in immunology · 2023Article
- ENPEP as a potential predictor of immune checkpoint inhibitor efficacy.Cancer medicine · 2022Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe gene ENPEP encodes glutamyl aminopeptidase, which can cut N-terminal aspartic acid from angiotensin II, and is related to tumorigenesis and immune microenvironment, however, the association between the expression of ENPEP and benefits of immune checkpoint inhibitors (ICIs) has had no investigation.
methodsWe assess the immunotherapeutic predictive performance of ENPEP expression and mutation in multiple cohorts, including one discovery cohort (Pender cohort), four validation cohorts (Hugo cohort; Liu cohort; Mariathasan cohort; Zhao cohort), and one mutation cohort (Miao cohort). Cohorts from The Cancer Genome Atlas (TCGA) were used to explore mechanism and analysis prognosis.
resultsIn the discovery cohort, patients with lower ENPEP expression had superior response rates (47.2% vs. 36.1%) and over-all survival (OS) (HR [95% CI] = 0.61 [0.39-0.96]; p = 0.032) compared with those with higher ENPEP expression. The association between ENPEP and immunotherapy efficacy was consistently observed in validation cohorts (Hugo: OS HR [95% CI] = 0.41 [0.11-1.45], p = 0.158; Liu: OS HR [95% CI] = 0.73 [0.44-1.20], p = 0.211; Mariathasan: OS HR [95% CI] = 0.84 [0.65-1.09], p = 0.181; Zhao: OS HR [95% CI] = 0.20 [0.04-1.01], p = 0.033; Pooled cohort: OS HR [95% CI] = 0.76 [0.61-0.95], p = 0.015), and in the mutation cohort (ENPEP mutation vs. wild type (WT), OS HR [95% CI] = 0.46 [0.26-0.93], p = 0.017). Reliably, ENPEP is associated with M2 macrophage infiltration and activation in TCGA.
conclusionsOur results demonstrated ENPEP is a potential biomarker to classify patients' response to ICIs treatment.
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