Background: This study aimed to show that SHOX2 DNA methylation is a tumor marker in patients with suspected lung cancer by using bronchial fluid aspirated during bronchoscopy. Such a biomarker would be clinically valuable, especially when, following the first bronchoscopy, a final diagnosis cannot be established by histology or cytology. A test with a low false positive rate can reduce the need for further invasive and costly procedures and ensure early treatment.
Methods: Marker discovery was carried out by differential methylation hybridization (DMH) and real-time PCR. The real-time PCR based HeavyMethyl technology was used for quantitative analysis of DNA methylation of SHOX2 using bronchial aspirates from two clinical centres in a case-control study. Fresh-frozen and Saccomanno-fixed samples were used to show the tumor marker performance in different sample types of clinical relevance.
Results: Valid measurements were obtained from a total of 523 patient samples (242 controls, 281 cases). DNA methylation of SHOX2 allowed to distinguish between malignant and benign lung disease, i.e. abscesses, infections, obstructive lung diseases, sarcoidosis, scleroderma, stenoses, at high specificity (68% sensitivity [95% CI 62-73%], 95% specificity [95% CI 91-97%]).
Conclusions: Hypermethylation of SHOX2 in bronchial aspirates appears to be a clinically useful tumor marker for identifying subjects with lung carcinoma, especially if histological and cytological findings after bronchoscopy are ambiguous.
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http://dx.doi.org/10.1186/1471-2407-10-600 | DOI Listing |
Cell Rep
January 2025
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:
Chromatin regulatory proteins are expressed broadly and assumed to exert the same intrinsic function across cell types. Here, we report that 14 chromatin regulators undergo evolutionary-conserved neuron-specific splicing events involving microexons. Among them are two components of a histone demethylase complex: LSD1 H3K4 demethylase and the H3K4me0-reader PHF21A.
View Article and Find Full Text PDFImmun Inflamm Dis
January 2025
Second Department of Oncology, Guangdong Second Provincial General Hospital, Guangzhou, China.
Background: SET domain-containing protein 4 (SETD4) is a histone methyltransferase that has been shown to modulate cell proliferation, differentiation, and inflammatory responses by regulating histone H4 trimethylation (H4K20me3). Previous reports have demonstrated its function in the quiescence of cancer stem cells as well as drug resistance in several cancers. A limited number of systematic studies have examined SETD4's role in the tumor microenvironment, pathogenesis, prognosis, and therapeutic response.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Molecular Genetics and Genomics, New England Biolabs, Inc, 240 County Road, Ipswich, MA 01938, USA.
Gene expression is regulated by chromatin DNA methylation and other features, including histone post-translational modifications (PTMs), chromatin remodelers and transcription factor occupancy. A complete understanding of gene regulation will require the mapping of these chromatin features in small cell number samples. Here we describe a novel genome-wide chromatin profiling technology, named as Nicking Enzyme Epitope targeted DNA sequencing (NEED-seq).
View Article and Find Full Text PDFCancer Med
January 2025
Cancer Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Background: This study aims to elucidate the expression pattern of SERPINE1, assess its prognostic significance, and explore potential therapeutic drugs targeting this molecule.
Methods And Results: In this study, we delved into the variations in gene mutation, methylation patterns, and expression levels of SERPINE1 in head and neck squamous cell carcinoma (HNSCC) and normal tissues, leveraging comprehensive analyses of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The connection between the biological function of the gene and prognosis was scrutinized through immune infiltration and enrichment analyses.
R Soc Open Sci
January 2025
Department of Forensic Medicine, School of Basic Medical Sciences, Central South University, No172. Tongzipo Road, Changsha, Hunan 410013, People's Republic of China.
DNA mixtures containing semen and vaginal fluid are common biological samples in forensic analysis. However, the analysis of semen-vaginal fluid mixtures remains challenging. In this study, to solve these problems, it is proposed to combine semen-specific CpG sites and closely related microhaplotype sites to form a new composite genetic marker (semen-specific methylation-microhaplotype).
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