Epigenomic profiling of non-small cell lung cancer xenografts uncover LRP12 DNA methylation as predictive biomarker for carboplatin resistance

Genome Medicine
Sabrina GrasseMichal R Schweiger

Abstract

Non-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. Here, 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. Comprehensive 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 ...Continue Reading

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Citations

Sep 4, 2019·International Journal of Cancer. Journal International Du Cancer·Jiahao ShiXianqun Fan
Mar 12, 2020·Cancer Chemotherapy and Pharmacology·Soo Jin KimKeon Wook Kang
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Aug 7, 2021·Environmental Science and Pollution Research International·Ahmed ElfadadnyMohamed Elbadawy

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Methods Mentioned

BETA
xenograft
PCR
MeDIP-Seq
immunoprecipitation
Assay
PCA
Methyl-Seq
DNA assay
xenografts
PCRs

Software Mentioned

IPA
bowtie2
lumi
Illumina GenomeStudio
MeDIP
Eureka
galore
R
Ingenuity Pathway Analysis
db Bioconductor

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