Lung Cancer Diagnosis by Detecting Epigenetic Imprinting Alterations in Bronchoalveolar Lavage

Lung Cancer Clinical Trial

Official title:

A Multicenter Study for Evaluating the Benign and Malignant Pulmonary Noldules by Detecting the Epigenetic Imprinting Alterations in Bronchoalveolar Lavage

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05707585
• Other study ID #: LungCancerImprintingDiagnosis
• Status: Recruiting
• Start date: January 29, 2023
• Est. completion date: July 15, 2024

Study information

• Verified date: January 2023
• Source: The Second Affiliated Hospital of Dalian Medical University
• Contact: Encheng Li, MD
• Phone: +86-411-84671291
• Email: doctorliencheng[@]163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2064
• Est. completion date: July 15, 2024
• Est. primary completion date: January 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms

Intervention

Diagnostic Test:
• Quantitative Chromogenic Imprinted Gene in situ Hybridization (QCIGISH)
Visualize and quantify the allelic expression status of imprinted genes by in situ hybridization using probes targeting the nascent RNAs

Locations

Country	Name	City	State
China	The Second Affiliated Hospital of Dalian Medical University	Dalian	Liaoning
China	Zongda Hospital affiliated to Southeast University	Nanjing	Jiangsu
China	Zhongshan Hospital Fudan University	Shanghai

Sponsors (9)

Lead Sponsor	Collaborator
The Second Affiliated Hospital of Dalian Medical University	First Hospital of China Medical University, Fudan University, Henan Provincial People's Hospital, Lisen Imprinting Diagnostics, Inc., Shengjing Hospital, The First Affiliated Hospital of Guangzhou Medical University, West China Hospital, Zongda Hospital affiliated to Southeast University

Country where clinical trial is conducted

China, 

References & Publications (8)

Bartolomei MS, Tilghman SM. Genomic imprinting in mammals. Annu Rev Genet. 1997;31:493-525. doi: 10.1146/annurev.genet.31.1.493. — View Citation

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. — View Citation

Jelinic P, Shaw P. Loss of imprinting and cancer. J Pathol. 2007 Feb;211(3):261-8. doi: 10.1002/path.2116. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Epigenetic Imprinting Diagnostic Score	Cancer risk scores calculated by combining the biallelic expressions, multiallelic expressions and total expressions of several imprinted genes	Within 10 days after each sample collected