Methylation-specific PCR Test for Early Screening and Early Diagnosis of Nasopharyngeal Carcinoma
NCT ID: NCT06367049
Last Updated: 2024-04-16
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
470 participants
OBSERVATIONAL
2023-06-01
2024-03-01
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
DNA methylation is a form of chemical modification of DNA that can be done without altering the DNA sequence changes in genetic expression. The main role of DNA methylation is to regulate gene expression. Tumor suppressor genes play the functions of regulating cell differentiation, maturation and programmed death. However, if methylation of promoter region occurs, the expression of tumor suppressor genes is inhibited and the function is lost, resulting in cells remaining in the stage of low differentiation and proliferation, inhibition of apoptosis, formation of blood vessels by cluster cells, loss of cell adhesion, and formation of tumors. It can be seen that DNA methylation occurs in the early stage of tumor, and this biological feature makes it a strong application prospect in early tumor screening.
There are many methods to detect DNA Methylation, among which methylation-specific PCR (MSP) can easily and quickly determine the methylation status of a specific gene, meeting the affordable, convenient, and easy to generalize characteristics required for screening tests. In combination with previous MSP experiments and previous reports, we found that the methylation levels of promoter fragments of H4C6, Septin9 and RASSF1A genes in nasopharyngeal carcinoma tissues were significantly higher than those in healthy human nasopharyngeal tissues. This suggests that methylation of these three genes may be used as biomarkers for early screening and diagnosis of nasopharyngeal carcinoma.
Therefore, this study intends to detect the methylation status of H4C6, Septin9 and RASSF1A genes based on MSP method with simple operation and low cost. Using clinicopathological diagnosis as the gold standard, the value of this gene methylation index in early screening and early diagnosis of nasopharyngeal cancer was verified, providing a new detection index and method for improving the early diagnosis rate of nasopharyngeal cancer.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Nasopharyngeal Carcinoma Screening in Zhongshan City
NCT02501993
A Bidirectional Study in Exploring the Dynamic Changes of Plasma and Urine Metabolites of Nasopharyngeal Carcinoma.
NCT05682703
Comparison of Multi-omics Models for Early Nasopharyngeal Carcinoma Screening: CfDNA Methylation, EBV DNA, and Serological Double-antibodies Detection
NCT06763289
Prospective Study for Molecular Biomarkers of Normal Nasopharyngeal Tissue
NCT03048305
The Value of Diagnosis and Outcome Prediction in CTC for Metastatic NPC Patients
NCT02505139
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
CASE_CONTROL
PROSPECTIVE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Patient group
Sampling their nasopharyngeal swab specimens and peripheral blood specimens.
Methylation-specific PCR
Methylation-specific PCR is the simplest and quickest method for qualitative detection of methylation status.
The unmethylated C base is converted to U by bisulfite conversion, which is subsequently amplified by PCR with primers (methylation-specific and non-methylation-specific primers) and subsequently detected by agarose gel electrophoresis or a probe. The key to MSP is to design PCR primers for specific gene regions. The research team of this project has previously found the sequence sites of methylation of H4C6, Septin9 and RASSF1A genes in nasopharyngeal carcinoma tissues through methylation sequencing, and designed specific MSP amplification primers and probes accordingly, which can perform methylation detection easily and quickly.
Non-patient group
Sampling their nasopharyngeal swab specimens and peripheral blood specimens.
Methylation-specific PCR
Methylation-specific PCR is the simplest and quickest method for qualitative detection of methylation status.
The unmethylated C base is converted to U by bisulfite conversion, which is subsequently amplified by PCR with primers (methylation-specific and non-methylation-specific primers) and subsequently detected by agarose gel electrophoresis or a probe. The key to MSP is to design PCR primers for specific gene regions. The research team of this project has previously found the sequence sites of methylation of H4C6, Septin9 and RASSF1A genes in nasopharyngeal carcinoma tissues through methylation sequencing, and designed specific MSP amplification primers and probes accordingly, which can perform methylation detection easily and quickly.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Methylation-specific PCR
Methylation-specific PCR is the simplest and quickest method for qualitative detection of methylation status.
The unmethylated C base is converted to U by bisulfite conversion, which is subsequently amplified by PCR with primers (methylation-specific and non-methylation-specific primers) and subsequently detected by agarose gel electrophoresis or a probe. The key to MSP is to design PCR primers for specific gene regions. The research team of this project has previously found the sequence sites of methylation of H4C6, Septin9 and RASSF1A genes in nasopharyngeal carcinoma tissues through methylation sequencing, and designed specific MSP amplification primers and probes accordingly, which can perform methylation detection easily and quickly.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Age ≥18 years and ≤70 years.
3. No previous history of other tumors, and no current tumors.
Exclusion Criteria
2. There are serious medical complications, dysfunction of important organs (heart, lung, liver, kidney) or neuropsychiatric disorders.
3. Other patients or volunteers deemed unsuitable for inclusion by the supervising physician.
18 Years
70 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Guangdong Women and Children Hospital
OTHER
Affiliated Cancer Hospital & Institute of Guangzhou Medical University
OTHER
Sun Yat-sen University
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
YiJun Hua
Chief Physician
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Yi-Jun Hua, Phd
Role: PRINCIPAL_INVESTIGATOR
Sun Yat-sen University
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Sun yat-sen University Cancer Center
Guangzhou, Guangdong, China
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Karimi M, Johansson S, Stach D, Corcoran M, Grander D, Schalling M, Bakalkin G, Lyko F, Larsson C, Ekstrom TJ. LUMA (LUminometric Methylation Assay)--a high throughput method to the analysis of genomic DNA methylation. Exp Cell Res. 2006 Jul 1;312(11):1989-95. doi: 10.1016/j.yexcr.2006.03.006. Epub 2006 Apr 19.
Lyu JY, Chen JY, Zhang XJ, Zhang MW, Yu GS, Zhang L, Wen Z. Septin 9 Methylation in Nasopharyngeal Swabs: A Potential Minimally Invasive Biomarker for the Early Detection of Nasopharyngeal Carcinoma. Dis Markers. 2020 May 5;2020:7253531. doi: 10.1155/2020/7253531. eCollection 2020.
Chang HW, Chan A, Kwong DL, Wei WI, Sham JS, Yuen AP. Evaluation of hypermethylated tumor suppressor genes as tumor markers in mouth and throat rinsing fluid, nasopharyngeal swab and peripheral blood of nasopharygeal carcinoma patient. Int J Cancer. 2003 Jul 20;105(6):851-5. doi: 10.1002/ijc.11162.
Wong TS, Kwong DL, Sham JS, Wei WI, Kwong YL, Yuen AP. Quantitative plasma hypermethylated DNA markers of undifferentiated nasopharyngeal carcinoma. Clin Cancer Res. 2004 Apr 1;10(7):2401-6. doi: 10.1158/1078-0432.ccr-03-0139.
Hutajulu SH, Indrasari SR, Indrawati LP, Harijadi A, Duin S, Haryana SM, Steenbergen RD, Greijer AE, Middeldorp JM. Epigenetic markers for early detection of nasopharyngeal carcinoma in a high risk population. Mol Cancer. 2011 May 2;10:48. doi: 10.1186/1476-4598-10-48.
Ye M, Huang T, Ni C, Yang P, Chen S. Diagnostic Capacity of RASSF1A Promoter Methylation as a Biomarker in Tissue, Brushing, and Blood Samples of Nasopharyngeal Carcinoma. EBioMedicine. 2017 Apr;18:32-40. doi: 10.1016/j.ebiom.2017.03.038. Epub 2017 Apr 2.
Li Y, Yang X, Du X, Lei Y, He Q, Hong X, Tang X, Wen X, Zhang P, Sun Y, Zhang J, Wang Y, Ma J, Liu N. RAB37 Hypermethylation Regulates Metastasis and Resistance to Docetaxel-Based Induction Chemotherapy in Nasopharyngeal Carcinoma. Clin Cancer Res. 2018 Dec 15;24(24):6495-6508. doi: 10.1158/1078-0432.CCR-18-0532. Epub 2018 Aug 21.
Shi F, Zhou M, Shang L, Du Q, Li Y, Xie L, Liu X, Tang M, Luo X, Fan J, Zhou J, Gao Q, Qiu S, Wu W, Zhang X, Bode AM, Cao Y. EBV(LMP1)-induced metabolic reprogramming inhibits necroptosis through the hypermethylation of the RIP3 promoter. Theranostics. 2019 Apr 13;9(9):2424-2438. doi: 10.7150/thno.30941. eCollection 2019.
Zhao Y, Hong XH, Li K, Li YQ, Li YQ, He SW, Zhang PP, Li JY, Li Q, Liang YL, Chen Y, Ma J, Liu N, Chen YP. ZNF582 hypermethylation promotes metastasis of nasopharyngeal carcinoma by regulating the transcription of adhesion molecules Nectin-3 and NRXN3. Cancer Commun (Lond). 2020 Dec;40(12):721-737. doi: 10.1002/cac2.12104. Epub 2020 Oct 10.
Chen Y, Zhao Y, Yang X, Ren X, Huang S, Gong S, Tan X, Li J, He S, Li Y, Hong X, Li Q, Ding C, Fang X, Ma J, Liu N. USP44 regulates irradiation-induced DNA double-strand break repair and suppresses tumorigenesis in nasopharyngeal carcinoma. Nat Commun. 2022 Jan 25;13(1):501. doi: 10.1038/s41467-022-28158-2.
Papanicolau-Sengos A, Aldape K. DNA Methylation Profiling: An Emerging Paradigm for Cancer Diagnosis. Annu Rev Pathol. 2022 Jan 24;17:295-321. doi: 10.1146/annurev-pathol-042220-022304. Epub 2021 Nov 4.
Roy D, Tiirikainen M. Diagnostic Power of DNA Methylation Classifiers for Early Detection of Cancer. Trends Cancer. 2020 Feb;6(2):78-81. doi: 10.1016/j.trecan.2019.12.006. Epub 2020 Feb 3.
Widschwendter M, Zikan M, Wahl B, Lempiainen H, Paprotka T, Evans I, Jones A, Ghazali S, Reisel D, Eichner J, Rujan T, Yang Z, Teschendorff AE, Ryan A, Cibula D, Menon U, Wittenberger T. The potential of circulating tumor DNA methylation analysis for the early detection and management of ovarian cancer. Genome Med. 2017 Dec 22;9(1):116. doi: 10.1186/s13073-017-0500-7.
Sung CK, Yim H. CRISPR-mediated promoter de/methylation technologies for gene regulation. Arch Pharm Res. 2020 Jul;43(7):705-713. doi: 10.1007/s12272-020-01257-8. Epub 2020 Jul 28.
Mattei AL, Bailly N, Meissner A. DNA methylation: a historical perspective. Trends Genet. 2022 Jul;38(7):676-707. doi: 10.1016/j.tig.2022.03.010. Epub 2022 Apr 30.
Ji MF, Sheng W, Cheng WM, Ng MH, Wu BH, Yu X, Wei KR, Li FG, Lian SF, Wang PP, Quan W, Deng L, Li XH, Liu XD, Xie YL, Huang SJ, Ge SX, Huang SL, Liang XJ, He SM, Huang HW, Xia SL, Ng PS, Chen HL, Xie SH, Liu Q, Hong MH, Ma J, Yuan Y, Xia NS, Zhang J, Cao SM. Incidence and mortality of nasopharyngeal carcinoma: interim analysis of a cluster randomized controlled screening trial (PRO-NPC-001) in southern China. Ann Oncol. 2019 Oct 1;30(10):1630-1637. doi: 10.1093/annonc/mdz231.
Zhang MX, Li J, Shen GP, Zou X, Xu JJ, Jiang R, You R, Hua YJ, Sun Y, Ma J, Hong MH, Chen MY. Intensity-modulated radiotherapy prolongs the survival of patients with nasopharyngeal carcinoma compared with conventional two-dimensional radiotherapy: A 10-year experience with a large cohort and long follow-up. Eur J Cancer. 2015 Nov;51(17):2587-95. doi: 10.1016/j.ejca.2015.08.006. Epub 2015 Aug 26.
Zeng Y, Zhang LG, Wu YC, Huang YS, Huang NQ, Li JY, Wang YB, Jiang MK, Fang Z, Meng NN. Prospective studies on nasopharyngeal carcinoma in Epstein-Barr virus IgA/VCA antibody-positive persons in Wuzhou City, China. Int J Cancer. 1985 Nov 15;36(5):545-7. doi: 10.1002/ijc.2910360505.
Liu YP, Lv X, Zou X, Hua YJ, You R, Yang Q, Xia L, Guo SY, Hu W, Zhang MX, Chen SY, Lin M, Xie YL, Liu LZ, Sun R, Huang PY, Fan W, Guo X, Hong MH, Chen MY. Minimally invasive surgery alone compared with intensity-modulated radiotherapy for primary stage I nasopharyngeal carcinoma. Cancer Commun (Lond). 2019 Nov 15;39(1):75. doi: 10.1186/s40880-019-0415-3.
Chan KCA, Woo JKS, King A, Zee BCY, Lam WKJ, Chan SL, Chu SWI, Mak C, Tse IOL, Leung SYM, Chan G, Hui EP, Ma BBY, Chiu RWK, Leung SF, van Hasselt AC, Chan ATC, Lo YMD. Analysis of Plasma Epstein-Barr Virus DNA to Screen for Nasopharyngeal Cancer. N Engl J Med. 2017 Aug 10;377(6):513-522. doi: 10.1056/NEJMoa1701717.
Chan KC, Lo YM. Circulating EBV DNA as a tumor marker for nasopharyngeal carcinoma. Semin Cancer Biol. 2002 Dec;12(6):489-96. doi: 10.1016/s1044579x02000913.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2023-FXY-230-NPC
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.