The patients receive the surgery according to the indication of surgery. The diagnosis is confirmed by pathology of removed tissue. The result of imprinting detection are used as cancer group.

Patients ruled out the possibility of malignancy according to biopsy pathology are used as negative control.

The loss of imprinting (LOI) and copy number variation (CNV) from biopsies will be tested by LiSen in-situ imprinting detection.

In-situ imprinting detection

Chunxue Bai, MD

Dawei Yang, MD

The current research focus for cancer diagonosis is classical genetics, named "driving genes". However, not all cancer patients have typical genetic alterations, especially at early stage. In the past dacades, accumulating evidences have revealed that more than 80% diseases are closely related to epigenetic changes. The normally silenced copy of imprinted genes are reactivated at early stage of cancers, and finally proceed to copy number variation. This study will screen for a panel of imprinted genes and build quantitative models to assist the diagnosis of multiple cancers.

This study collects biopsies samples including but not limited to bronchoscopy biopsy, bronchial lavage fluid, fine needle aspiration, cystoscopy biopsy, urine samples, colonoscopy biopsy.

Role of Genomic Imprinting in Cancer Diagnosis

Number of patients "declared positive" with the imprinting early detection among the patients suffered from cancer

Number of patients "declared negative" with the imprinting early detection among the patients who are with benign tumors or other diseases

Number of patients "declared positive" with the imprinting early detection versus patients "declared positive" with the cytopathology

Number of patients "declared negative" with the imprinting early detection versus patients "declared negative" with the cytopathology

LiSen Imprinting Diagnostic Inc.

Chinese Alliance Against Lung Cancer

Chair

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

All Drugs and Chemicals

Dimercaprol

Visualize and quantify the allelic expression status of imprinted genes by in situ hybridization using probes targeting the nascent RNAs

Quantitative Chromogenic Imprinted Gene in situ Hybridization (QCIGISH)

Encheng Li, MD

Ming Ding, MD

Jian Zhou, PhD

Qi Wang, MD

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.

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.

Lung Cancer Diagnosis by Detecting Epigenetic Imprinting Alterations in Bronchoalveolar Lavage

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

Cancer risk scores calculated by combining the biallelic expressions, multiallelic expressions and total expressions of several imprinted genes

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.

The Second Affiliated Hospital of Dalian Medical University

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Urinary Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Diagnosed bladder cancer patients who are being monitored will be the experimental group to develop the LOI panel, and subsequent cohort will be used to confirm the sensitivity and specificity of this urinary analysis.

Patients being treated for other diseases but without any tumor or healthy participants will provide a negative control to provide data for developing the LOI diagnostic panel

The changes of LOI The obtained LOI from morning urine and tumor will be tested by LiSen imprinting diagnostic (LSID)

Genomic Imprinting Testing

Shuxiong Zeng, M.D., Ph.D

Chuanliang Xu, M.D., Ph.D

Yinghao Sun, M.D., Ph.D

Chuangliang Xu, M.D., Ph.D

Urine analysis provide a promising non-invasive liquid biopsy for diagnosis of bladder cancer. Molecular biomarkers in urine may serve as important diagnostic and prognostic indicators for bladder cancer. Many alterations of genes and proteins have been identified in the urinary for diagnosis of bladder cancer. However, not all bladder cancer patients have the same alterations due to tumor heterogeneity. Thus, to reach satisfactory sensitivity and specificity a new diagnostic molecular alteration should exists ubiquitously in cancers. Numerous studies indicate that Loss of imprinting (LOI) exists ubiquitously in cancers and precede morphological changes. The investigators will conduct a prospective evaluation of a panel of LOI changes in urine test for detection and surveillance of bladder cancer patients.

During the progression of tumor, molecular changes in both genomics and epigenomics occur prior to morphological changes in cells and tissues, therefore molecular biological test is more sensitive to detect cancer at early stage. Genomic imprinting is one kind of epigenetic regulation that controls gene expression. In detail, a copy of gene on the certain maternal or paternal allele is silenced through methylation, while the other acts normally. This kind of genes are named imprinting genes. Loss of imprinting and Copy number variation (LOI \& CNV) is epigenetic change that the silenced copy of an imprinting gene is activated through demethylation. Numerous studies indicate that LOI exists ubiquitously in cancers and precede morphological changes. In contrast, LOI rarely happens in normal somatic cells. Therefore, the methylation status of imprinting genes can act as a biomarker to detect and analyze the abnormal cells.

The investigators will develop a couple of common LOI to establish a predictive diagnostic LOI panel in urine with optimal and robust efficacy in diagnosis of bladder cancer by analyzing LOI in urine from bladder cancer patients and control group that without any tumor in urinary system or other organs. Moreover, the changes of LOI in urine collected before and 1 year after transurethral resection of non-muscle invasive bladder cancer (NIMBC) will also be monitored. External consistency validation will be performed on subsequent urine from patients and control participants collection.

Loss of imprinting and Copy number variation (LOI \& CNV) is epigenetic change that the silenced copy of an imprinting gene is activated through demethylation. Numerous studies indicate that LOI exists ubiquitously in cancers and precede morphological changes. In contrast, LOI rarely happens in normal somatic cells. Therefore, the methylation status of imprinting genes can act as a biomarker to detect and analyze the abnormal cast-off cells in urine.

Genomic Imprinting Testing for Diagnosis of Bladder Cancer

Evaluation of Genomic Imprinting Testing for Detection and Surveillance of Bladder Cancer Patients

Number of patients "declared positive" with the LOI urine test among the patients suffered from bladder cancer

Number of patients "declared negative" with the LOI urine test among the patients who are without cancer

Number of patients "declared positive" with the LOI urine test after bladder cancer surgery among the patients being confirmed to have bladder cancer by cystoscopic examination and biopsy

Number of patients "declared negative" with the LOI urine test after bladder cancer surgery among the patients being confirmed to have no bladder cancer recurrence by cystoscopic examination

Number of patients "declared positive" with the LOI analysis versus patients "declared positive" with the urine cytology

Number of patients "declared negative" with the LOI analysis versus patients " declared negative " with the urine cytology

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Role of Genomic Imprinting in Cancer Diagnosis	NCT03882684	Early Diagnosis Cancer Biomarker Genomic Imprint...	In-situ imprint...	18 Years -	Chinese Alliance Against Lung Cancer
Lung Cancer Diagnosis by Detecting Epigenetic Imprinting Alterations in Bronchoalveolar Lavage	NCT05707585	Lung Cancer	Quantitative Ch...	18 Years - 75 Years	The Second Affiliated Hospital of Dalian Medical University
Genomic Imprinting Testing for Diagnosis of Bladder Cancer	NCT03563443	Bladder Cancer Urine Marking Diagnoses Disea...	Genomic Imprint...	18 Years -	Changhai Hospital
Lung Cancer Diagnosis by Detecting Epigenetic Imprinting Alterations in Bronchoalveolar Lavage	NCT05707585	Lung Cancer	Quantitative Ch...	18 Years - 75 Years	The Second Affiliated Hospital of Dalian Medical University
Genomic Imprinting Testing for Diagnosis of Bladder Cancer	NCT03563443	Bladder Cancer Urine Marking Diagnoses Disea...	Genomic Imprint...	18 Years -	Changhai Hospital

Spots Global Cancer Trial Database for genomic imprinting