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POTEE mutation as a potential predictive biomarker for immune checkpoint inhibitors in lung adenocarcinoma

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Summary

Precise selection of patients who could benefit from immune checkpoint inhibitors (ICIs) is an important challenge for immunotherapy in lung cancer. POTEE (POTE Ankyrin Domain Family Member E) is a member of one primate-specific gene family which have been identified as cancer-related antigens and potential target for immunotherapy of cancer. Here, we investigated the correlation between POTEE mutation and the clinical outcome of ICIs treatment in non-small cell lung cancer (NSCLC). We merged three NSCLC cohorts (n = 165) to assess predictive value of POTEE mutation of immunotherapy efficacy in NSCLC. The prognostic analysis and the potential molecular mechanism exploration were conducted based on the data from The Cancer Genome Atlas (TCGA) database. In the merged cohort, patients with POTEE-mutation (POTEE-Mut) had a significantly higher objective response rate (ORR) (100% vs 27.7%; P < 0.001) and longer progression-free survival (PFS) (P = 0.001; HR 0.08; 95% CI 0.01 - 0.54) compared to patients with POTEE wild-type (POTEE-WT) in NSCLC. Also, patients with POTEE-Mut showed higher ORR (100% vs 27.2%; P < 0.001) and longer PFS (P = 0.001; HR 0.07; 95% CI 0.01 - 0.52) in lung adenocarcinoma (LUAD). POTEE mutation was significantly associated with higher tumor mutational burden (TMB) and higher neoantigen load (NAL), but not with PD-L1 expression in LUAD. Gene set enrichment analyses (GSEA) analysis revealed prominent enrichment of signatures related to DNA repair in POTEE-Mut group (P < 0.001) in LUAD. Our results indicate that POTEE mutation could serve as a potential predictive biomarker for ICIs in LUAD. However, prospective cohort studies are still needed for further validation.

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Data availability

All of the data used in this study were publicly available in cBioPortal and TCGA.

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Authors and Affiliations

  1. Center of Treatment of Myasthenia Gravis, Hebei Provincial Key Laboratory of Myasthenia Gravis, Hebei Provincial Clinical Research Center for Myasthenia gravis, People’s Hospital of Shijiazhuang affiliated to Hebei Medical University, Hebei, 050000, Shijiazhuang, China

    Yongzhao Li

  2. The Medical Department, The State Key Lab of Translational Medicine and Innovative Drug Development, Jiangsu Simcere Diagnostics Co., Ltd; Nanjing Simcere Medical Laboratory Science Co., Ltd, Jiangsu, 210002, Nanjing, China

    Qidong Yang, Yaqin Liu, Huan Yi & Yongzhi Ju

  3. Center of Treatment of Myasthenia Gravis, People’s Hospital of Shijiazhuang affiliated to Hebei Medical University, Hebei, 050000, Shijiazhuang, China

    Guoyan Qi

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Contributions

Yongzhao Li conceived the study. Qidong Yang and Yaqin Liu prepared the manuscript and the literature search. Huan Yi analyzed the data and prepared figures. Yongzhi Ju and Guoyan Qi reviewed and edited the manuscript. All authors contributed to the article and approved the submitted version.

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Correspondence to Guoyan Qi.

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Li, Y., Yang, Q., Liu, Y. et al. POTEE mutation as a potential predictive biomarker for immune checkpoint inhibitors in lung adenocarcinoma. Invest New Drugs 41, 556–563 (2023). https://doi.org/10.1007/s10637-023-01375-2

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