ArticleGenome medicine2018
Epigenomic profiling of non-small cell lung cancer xenografts uncover LRP12 DNA methylation as predictive biomarker for carboplatin resistance.
Article in Genome medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
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- LRP12 promotes gastric cancer progression through AKT/mTOR signaling and M2 macrophage-mediated immunosuppression.Scientific reports · 2025Article
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- Cancer, metastasis, and the epigenome.Molecular cancer · 2024Review
- Targeted inhibition of the PI3K/AKT/mTOR pathway by (+)-anthrabenzoxocinone induces cell cycle arrest, apoptosis, and autophagy in non-small cell lung cancer.Cellular & molecular biology letters · 2024Article
- Comprehensive Analysis of the Prognostic Marker and Immune Infiltrates of LDLR-Related Proteins Family Members in Breast Cancer.Iranian journal of pathology · 2024Article
- Link between m6A modification and infiltration characterization of tumor microenvironment in lung adenocarcinoma.Experimental biology and medicine (Maywood, N.J.) · 2023Article
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- Recent Multiomics Approaches in Endometrial Cancer.International journal of molecular sciences · 2022Review
- Breaking the crosstalk of the Cellular Tumorigenic Network by low-dose combination therapy in lung cancer patient-derived xenografts.Communications biology · 2022Article
- Clinicopathological implications of lncRNAs, immunotherapy and DNA methylation in lung squamous cell carcinoma: a narrative review.Translational cancer research · 2021Review
- Role of multidrug resistance-associated proteins in cancer therapeutics: past, present, and future perspectives.Environmental science and pollution research international · 2021Review
- Pericentromeric Satellite III transcripts induce etoposide resistance.Cell death & disease · 2021Article
- A novel DNA methylation-based model that effectively predicts prognosis in hepatocellular carcinoma.Bioscience reports · 2021Article
- EXT1 methylation promotes proliferation and migration and predicts the clinical outcome of non-small cell lung carcinoma via WNT signalling pathway.Journal of cellular and molecular medicine · 2021Article
- RNA methyltransferase METTL3 induces intrinsic resistance to gefitinib by combining with MET to regulate PI3K/AKT pathway in lung adenocarcinoma.Journal of cellular and molecular medicine · 2021Article
- MeImmS: Predict Clinical Benefit of Anti-PD-1/PD-L1 Treatments Based on DNA Methylation in Non-small Cell Lung Cancer.Frontiers in genetics · 2021Article
- An integrated epigenomic-transcriptomic landscape of lung cancer reveals novel methylation driver genes of diagnostic and therapeutic relevance.Theranostics · 2021Article
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Authors and funding
26 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundNon-small cell lung cancer (NSCLC) is the most common cause of cancer-related deaths worldwide and is primarily treated with radiation, surgery, and platinum-based drugs like cisplatin and carboplatin. The major challenge in the treatment of NSCLC patients is intrinsic or acquired resistance to chemotherapy. Molecular markers predicting the outcome of the patients are urgently needed.
methodsHere, we employed patient-derived xenografts (PDXs) to detect predictive methylation biomarkers for platin-based therapies. We used MeDIP-Seq to generate genome-wide DNA methylation profiles of 22 PDXs, their parental primary NSCLC, and their corresponding normal tissues and complemented the data with gene expression analyses of the same tissues. Candidate biomarkers were validated with quantitative methylation-specific PCRs (qMSP) in an independent cohort.
resultsComprehensive analyses revealed that differential methylation patterns are highly similar, enriched in PDXs and lung tumor-specific when comparing differences in methylation between PDXs versus primary NSCLC. We identified a set of 40 candidate regions with methylation correlated to carboplatin response and corresponding inverse gene expression pattern even before therapy. This analysis led to the identification of a promoter CpG island methylation of LDL receptor-related protein 12 (LRP12) associated with increased resistance to carboplatin. Validation in an independent patient cohort (n = 35) confirmed that LRP12 methylation status is predictive for therapeutic response of NSCLC patients to platin therapy with a sensitivity of 80% and a specificity of 84% (p < 0.01). Similarly, we find a shorter survival time for patients with LRP12 hypermethylation in the TCGA data set for NSCLC (lung adenocarcinoma).
conclusionsUsing an epigenome-wide sequencing approach, we find differential methylation patterns from primary lung cancer and PDX-derived cancers to be very similar, albeit with a lower degree of differential methylation in primary tumors. We identify LRP12 DNA methylation as a powerful predictive marker for carboplatin resistance. These findings outline a platform for the identification of epigenetic therapy resistance biomarkers based on PDX NSCLC models.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.