Clinical trial NCT05707585: Lung Cancer Diagnosis by Detecting Epigenetic Imprinting Alterations in Bronchoalveolar Lavage
Official title: A Multicenter Study for Evaluating the Benign and Malignant Pulmonary Noldules by Detecting the Epigenetic Imprinting Alterations in Bronchoalveolar Lavage
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Lung Cancer
Keywords: Genomic Imprinting
Epigenetics
Diagnostic Study
Bronchoalveolar Lavage
Lead sponsor: The Second Affiliated Hospital of Dalian Medical University
Sponsor class: OTHER
Collaborators: name: Fudan University
name: Zongda Hospital affiliated to Southeast University
name: West China Hospital
name: Henan Provincial People's Hospital
name: First Hospital of China Medical University
name: Shengjing Hospital
name: The First Affiliated Hospital of Guangzhou Medical University
name: Lisen Imprinting Diagnostics, Inc.
First posted: 2023-02-01
Enrollment: 2064
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with pulmonary nodules and meet the criteria of bronchoscopy examination

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.

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.

Eligibility 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.

Primary outcomes:
measure: Epigenetic Imprinting Diagnostic Score
timeFrame: Within 10 days after each sample collected
Secondary outcomes:
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Zongda Hospital affiliated to Southeast University
state: Jiangsu
city: Dalian
country: China
facility: The Second Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
Study officials:
affiliation: The Second Affiliated Hospital of Dalian Medical University
name: Qi Wang, MD
role: STUDY_DIRECTOR
References:
citation: Jelinic P, Shaw P. Loss of imprinting and cancer. J Pathol. 2007 Feb;211(3):261-8. doi: 10.1002/path.2116.
citation: Bartolomei MS, Tilghman SM. Genomic imprinting in mammals. Annu Rev Genet. 1997;31:493-525. doi: 10.1146/annurev.genet.31.1.493.
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.
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.
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.
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.
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. 2023 Feb 20;41(6):1296-1306. doi: 10.1200/JCO.22.00232. Epub 2022 Nov 15.
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.