Lung Cancer Diagnosis by Detecting Epigenetic Imprinting Alterations in Bronchoalveolar Lavage
Study Details
Study Description
Brief Summary
The goal of this multicenter observational study is to evaluate the lung cancer diagnostic value of epigenetic imprinting detection in bronchoalveolar lavage. This study will mainly focus on varifing the previously identified epigenetic imprinting biomarkers for lung cancer and upgrading and validating a lung cancer imprinting diagnostic model specifically for bronchoalveolar lavage. The lavage sample will be collected from each eligible paticipants under bronchialscopy and undergo QCIGISH detection to analyze the allelic expression status of imprinted genes. The QCIGISH detection results will be compared with the final surgical histopathology. No interventions will be taken according to the QCIGISH detection results.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
Bronchial biopsy and bursh are widely used in lung cancer diagnosis but not bronchoalveolar lavage because of its low sensitivity. As the molecular alterations usually occur before the morphological changes, genetic and epigenetic biomarkers will be helpful for early diagnosis of cancers. As an important epigenetic regulation in mammalian embryo development, genomic imprinting plays important roles in cancers. In normal post-natal somatic cells, imprinted genes are "silenced", that is mono-allelically expressed either from the maternal or paternal allele, while in cancers, some silenced imprinting genes' copies could be reactivated, leading to expressions from both alleles. The loss of monoallelic gene regulation is named loss of imprinting (LOI), and has been previously found in various human cancers. Our previous studies has identified several imprinted genes with elevated aberrant allelic expressions in lung cancer. A diagnostic model based on the epigenetic imprinting biomarkers achieved 99.1% sensitivity and 92.1% specificity. In this study, we will first verify the epigenetic imprinting biomarkers in bronchoalveolar lavage, and refine the previously developed diagnostic model specifically for lavage samples. The diagnostic model will be independently validated in a group of prospectively enrolled cases. This study will help to distinguish benign and malignant pulmonary nodules presurgically, and improve the early diagnosis of lung cancer.
Study Design
Outcome Measures
Primary Outcome Measures
- Epigenetic Imprinting Diagnostic Score [Within 10 days after each sample collected]
Cancer risk scores calculated by combining the biallelic expressions, multiallelic expressions and total expressions of several imprinted genes
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age ≥ 18 years old, and ≤ 75 years old;
-
Chest CT showed pulmonary nodule with diameter<3cm;
-
Subjects voluntarily participated and signed the informed consent form.
Exclusion Criteria:
-
Active massive hemoptysis;
-
Severe heart and lung dysfunction;
-
Severe arrhythmia;
-
Extreme exhaustion of general condition;
-
Coagulation dysfunction;
-
Acute attack of asthma;
-
Aortic aneurysm.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Zongda Hospital affiliated to Southeast University | Nanjing | Jiangsu | China | 210009 |
| 2 | The Second Affiliated Hospital of Dalian Medical University | Dalian | Liaoning | China | 116023 |
| 3 | Zhongshan Hospital Fudan University | Shanghai | China | 200032 |
Sponsors and Collaborators
- The Second Affiliated Hospital of Dalian Medical University
- Fudan University
- Zongda Hospital affiliated to Southeast University
- West China Hospital
- Henan Provincial People's Hospital
- First Hospital of China Medical University
- Shengjing Hospital
- The First Affiliated Hospital of Guangzhou Medical University
- Lisen Imprinting Diagnostics, Inc.
Investigators
- Study Director: Qi Wang, MD, The Second Affiliated Hospital of Dalian Medical University
Study Documents (Full-Text)
None provided.More Information
Publications
- Bartolomei MS, Tilghman SM. Genomic imprinting in mammals. Annu Rev Genet. 1997;31:493-525. doi: 10.1146/annurev.genet.31.1.493.
- Ito Y, Koessler T, Ibrahim AE, Rai S, Vowler SL, Abu-Amero S, Silva AL, Maia AT, Huddleston JE, Uribe-Lewis S, Woodfine K, Jagodic M, Nativio R, Dunning A, Moore G, Klenova E, Bingham S, Pharoah PD, Brenton JD, Beck S, Sandhu MS, Murrell A. Somatically acquired hypomethylation of IGF2 in breast and colorectal cancer. Hum Mol Genet. 2008 Sep 1;17(17):2633-43. doi: 10.1093/hmg/ddn163. Epub 2008 Jun 9.
- Jelinic P, Shaw P. Loss of imprinting and cancer. J Pathol. 2007 Feb;211(3):261-8. doi: 10.1002/path.2116.
- Matouk IJ, Halle D, Gilon M, Hochberg A. The non-coding RNAs of the H19-IGF2 imprinted loci: a focus on biological roles and therapeutic potential in Lung Cancer. J Transl Med. 2015 Apr 9;13:113. doi: 10.1186/s12967-015-0467-3.
- Ribarska T, Goering W, Droop J, Bastian KM, Ingenwerth M, Schulz WA. Deregulation of an imprinted gene network in prostate cancer. Epigenetics. 2014 May;9(5):704-17. doi: 10.4161/epi.28006. Epub 2014 Feb 10.
- Shen R, Cheng T, Xu C, Yung RC, Bao J, Li X, Yu H, Lu S, Xu H, Wu H, Zhou J, Bu W, Wang X, Si H, Shi P, Zhao P, Liu Y, Deng Y, Zhu Y, Zeng S, Pineda JP, Lin C, Zhou N, Bai C. Novel visualized quantitative epigenetic imprinted gene biomarkers diagnose the malignancy of ten cancer types. Clin Epigenetics. 2020 May 24;12(1):71. doi: 10.1186/s13148-020-00861-1.
- Xu H, Zhang Y, Wu H, Zhou N, Li X, Pineda JP, Zhu Y, Fu H, Ying M, Yang S, Bao J, Yang L, Zhang B, Guo L, Sun L, Lu F, Wang H, Huang Y, Zhu T, Wang X, Wei Q, Sheng C, Qu S, Lv Z, Xu D, Li Q, Dong Y, Qin J, Cheng T, Xing M. High Diagnostic Accuracy of Epigenetic Imprinting Biomarkers in Thyroid Nodules. J Clin Oncol. 2022 Nov 15:JCO2200232. doi: 10.1200/JCO.22.00232. Online ahead of print.
- Zhou J, Cheng T, Li X, Hu J, Li E, Ding M, Shen R, Pineda JP, Li C, Lu S, Yu H, Sun J, Huang W, Wang X, Si H, Shi P, Liu J, Chang M, Dou M, Shi M, Chen X, Yung RC, Wang Q, Zhou N, Bai C. Epigenetic imprinting alterations as effective diagnostic biomarkers for early-stage lung cancer and small pulmonary nodules. Clin Epigenetics. 2021 Dec 14;13(1):220. doi: 10.1186/s13148-021-01203-5.
- LungCancerImprintingDiagnosis