ArticleCell proliferation2022
PAPPA2 mutation as a novel indicator stratifying beneficiaries of immune checkpoint inhibitors in skin cutaneous melanoma and non-small cell lung cancer.
Article in Cell proliferation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 16 citations in OpenAlex.
- Targeting the Tumor Microenvironment Network to Overcome Immunotherapy Resistance in Non-Small Cell Lung Cancer: Mechanisms to Clinical Translation.Cancer medicine · 2026Review
- Identification of SLIT3 mutation as a response biomarker for immune checkpoint inhibitor therapy in non-small cell lung cancer.Discover oncology · 2026Article
- PTEN status on gonadotropin-releasing hormone (GnRH) metabolite, GnRH-(1-5), effects in endometrial cancer cell lines migration, & transcriptomic analysis of basal cell line and tumor gene expressions†.Biology of reproduction · 2025Article
- DNA methylation and transcription factor-driven immune subtypes in ovarian cancer.Discover oncology · 2025Article
- DYNC2H1 mutation as a potential predictive biomarker for immune checkpoint inhibitor efficacy in NSCLC and melanoma.Investigational new drugs · 2025Article
- Integrating genomic mutations and tumor-infiltrating lymphocytes improves prediction of response to trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer.Cancer drug resistance (Alhambra, Calif.) · 2025Article
- Genomic regions associated with bovine respiratory disease in pacific northwest Holstein cattle.Frontiers in veterinary science · 2025Article
- Predictive value of ZFHX4 mutation for the efficacy of immune checkpoint inhibitors in non-small cell lung cancer and melanoma.Investigational new drugs · 2024Article
- Transcriptome Analysis Reveals Distinct Patterns Between the Invasive and Noninvasive Pituitary Neuroendocrine Tumors.Journal of the Endocrine Society · 2024Article
- TG468: a text graph convolutional network for predicting clinical response to immune checkpoint inhibitor therapy.Briefings in bioinformatics · 2024Article
- PAPPA2 mutation as a novel indicator stratifying beneficiaries of immune checkpoint inhibitors in skin cutaneous melanoma and non-small cell lung cancer.Cell proliferation · 2022Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPappalysin 2 (PAPPA2) mutation, occurring most frequently in skin cutaneous melanoma (SKCM) and non-small cell lung cancer (NSCLC), is found to be related to anti-tumour immune response. However, the association between PAPPA2 and the efficacy of immune checkpoint inhibitors (ICIs) therapy remains unknown.
methodsTo analyse the performance of PAPPA2 mutation as an indicator stratifying beneficiaries of ICIs, seven public cohorts with whole-exome sequencing (WES) data were divided into the NSCLC set (n = 165) and the SKCM set (n = 210). For further validation, 41 NSCLC patients receiving anti-PD-(L)1 treatment were enrolled in China cohort (n = 41). The mechanism was explored based on The Cancer Genome Atlas database (n = 1467).
resultsIn the NSCLC set, patients with PAPPA2 mutation (PAPPA2-Mut) demonstrated a significantly superior progress free survival (PFS, hazard ratio [HR], 0.28 [95% CI, 0.14-0.53]; p < 0.001) and objective response rate (ORR, 77.8% vs. 23.2%; p < 0.001) compared to those with wide-type PAPPA2 (PAPPA2-WT), consistent in the SKCM set (overall survival, HR, 0.49 [95% CI: 0.31-0.78], p < 0.001; ORR, 34.1% vs. 16.9%, p = 0.039) and China cohort. Similar results were observed in multivariable models. Accordingly, PAPPA2 mutation exhibited superior performance in predicting ICIs efficacy compared with other published ICIs-related gene mutations, such as EPHA family, MUC16, LRP1B and TTN, etc. In addition, combined utilization of PAPPA2 mutation and tumour mutational burden (TMB) could expand the identification of potential responders to ICIs therapy in both NSCLC set (HR, 0.36 [95% CI: 0.23-0.57], p < 0.001) and SKCM set (HR, 0.51 [95% CI: 0.34-0.76], p < 0.001). Moreover, PAPPA2 mutation was correlated with enhanced anti-tumour immunity including higher activated CD4 memory T cells level, lower Treg cells level, and upregulated DNA damage repair pathways.
conclusionsOur findings indicated that PAPPA2 mutation could serve as a novel indicator to stratify beneficiaries from ICIs therapy in NSCLC and SKCM, warranting further prospective studies.
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