scholarly journals Noninvasive Diagnostics for Early Detection of Lung Cancer: Challenges and Potential with a Focus on Changes in DNA Methylation

2020 ◽  
Vol 29 (12) ◽  
pp. 2416-2422
Author(s):  
Maria Farooq ◽  
James G. Herman
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Early Detection ◽  
Noninvasive Diagnostics

scholarly journals High-Throughput Detection of Multiple miRNAs and Methylated DNA by Droplet Digital PCR

2021 ◽  
Vol 11 (5) ◽  
pp. 359
Author(s):  
Ning Li ◽  
Pushpa Dhilipkannah ◽  
Feng Jiang
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Early Detection ◽  
Cancer Patients ◽  
High Throughput ◽  
Digital Pcr ◽  
Droplet Digital Pcr ◽  
Lung Cancer Patients ◽  
Molecular Aberrations ◽  
High Throughput Assay

Altered miRNA expression and DNA methylation have highly active and diverse roles in carcinogenesis. Simultaneous detection of the molecular aberrations may have a synergistic effect on the diagnosis of malignancies. Herein, we develop a high-throughput assay for detecting multiple miRNAs and DNA methylation using droplet digital PCR (ddPCR) coupled with a 96-microwell plate. The microplate-based ddPCR could absolutely and reproducibly quantify 15 miRNAs and 14 DNA methylation sites with a high sensitivity (one copy/µL and 0.1%, respectively). Analyzing sputum and plasma of 40 lung cancer patients and 36 cancer-free smokers by this approach identified an integrated biomarker panel consisting of two sputum miRNAs (miRs-31-5p and 210-3p), one sputum DNA methylation (RASSF1A), and two plasma miRNAs (miR-21-5p and 126) for the diagnosis of lung cancer with higher sensitivity and specificity compared with a single type of biomarker. The diagnostic value of the integrated biomarker panel for the early detection of lung cancer was confirmed in a different cohort of 36 lung cancer patients and 39 cancer-free smokers. The high-throughput assay for quantification of multiple molecular aberrations across sputum and plasma could improve the early detection of lung cancer.

Cell-free DNA methylation markers for noninvasive early detection of nasopharyngeal carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14537-e14537
Author(s):  
Dhruvajyoti Roy ◽  
David J Taggart ◽  
Lianghong Zheng ◽  
Dan Liu ◽  
Gen Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Nasopharyngeal Carcinoma ◽  
Early Detection ◽  
Stage Iv ◽  
Stage I ◽  
The Arctic ◽  
Cell Free Dna ◽  
Methylation Marker ◽  
Free Dna

e14537 Background: Nasopharyngeal carcinoma (NPC) is one of the most prevalent malignancies among populations native to Southeast Asia, the Mediterranean Basin and the Arctic. Early diagnosis of NPC is predicted to improve survival. The identification of cancer-specific DNA methylation patterns of cell-free DNA (cfDNA) isolated from blood samples is an established approach for detecting various cancers. In the present study, we evaluated the performance characteristics of a previously identified NPC methylation marker panel for the diagnosis of nasopharyngeal carcinoma. Methods: Retrospective samples were obtained for 168 subjects, including: 59 subjects diagnosed with NPC (Stage I to IV), 14 subjects diagnosed with benign nasopharyngeal disease and 43 healthy subjects. In addition, sample were obtained for 52 subjects diagnosed with breast, colorectal, liver or lung cancer. Samples were provided to the laboratory blinded for DNA methylation analysis by using the IvyGene Platform. Results: A total of 57 of the 59 samples drawn from subjects with NPC were correctly identified for an overall sensitivity of 97%, with little difference between the sensitivity of detecting Stage I to Stage IV nasopharyngeal carcinoma (range 92% to 100%). For subjects diagnosed with other cancers, 85% of colorectal cancer samples, 82% of lung cancer samples, 93% of both breast cancer and liver cancer samples, were correctly identified as negative for NPC, for a total calculated analytical specificity of 86%. Additionally, all 43 samples drawn from healthy donors and 14 samples drawn from subjects diagnosed with benign nasopharyngeal disease were correctly identified as negative for nasopharyngeal carcinoma for a combined specificity of 100%. Conclusions: The NPC methylation panel was demonstrated to be both sensitive and specific for the detection of nasopharyngeal carcinoma. The potential of cfDNA methylation markers for the early detection of nasopharyngeal carcinoma is predicted to improve patient outcomes through earlier detection of the disease.

scholarly journals THE POTENTIAL OF CELL-FREE DNA METHYLATION BIOMARKER AS AN EARLY DETECTION FOR LUNG CANCER

2021 ◽  
Vol 9 (1) ◽  
pp. 77-89
Author(s):  
Muhammad Yusuf ◽  
Nasim Amar ◽  
Shintya Octaviana Baliulina
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Tumor Suppressor ◽  
Early Detection ◽  
Tumor Suppressor Gene ◽  
False Positive ◽  
Suppressor Gene ◽  
Cochrane Library ◽  
Cell Free Dna ◽  
Free Dna

Pendahuluan: Kanker paru masih menjadi penyebab utama kematian akibat kanker. Metode skrining terkini masih memiliki banyak kekurangan dalam mendiagnosis kanker paru, sehingga dibutuhkan metode skrining yang lebih cermat dan aplikatif dalam mendiagnosis individu dengan kanker paru. Salah satu metode skrining yang berpotensi membantu penegakkan diagnosis kanker paru adalah metilasi DNA yang diduga memiliki keunggulan sebagai biomarka pada kanker paru. Metode: Pencarian dan seleksi jurnal sesuai kriteria inklusi melalui database PubMed, ScienceDirect, dan Cochrane Library. Ditemukan sejumlah 13 studi yang memenuhi kriteria inklusi. Pembahasan: Metilasi DNA terjadi pada fase awal perkembangan kanker dan bersifat spesifik pada jenis tumor yang berbeda. Pada kanker paru, regulasi DNA metiltransferase (DNMT) dan enzim ten-eleven translocation (TET) mengalami disrupsi sehingga terjadi inaktivasi tumor suppressor gene dan perkembangan kanker. Secara keseluruhan, metilasi DNA pada gen HOXD10 / PAX9 / PTPRN2 / STAG3,  SHOX2 / PTGER4 / FOXL2, SOX17 / TAC1 / HOXA7 / CDO1 / HOXA9 / ZFP42, dan CDO1 / SOX17 / HOXA7 memiliki sensitivitas hingga >90%. Beberapa panel metilasi DNA lainnya seperti DCC, TMEM196, SHOX2 / PTGER4, dan CDO1 / SOX17 / HOXA7 memiliki spesifisitas yang tinggi hingga 90-100%. Selain itu, nilai AUC menunjukan angka diatas 0,80 pada mayoritas studi. Metilasi DNA sebagai penunjang metode skrining dapat meningkatkan efektivitas deteksi dini dan dapat menurunkan tingkat false positive. Simpulan: Biomarka metilasi DNA efektif sebagai metode deteksi dini kanker paru.

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