Digestive System Diseases

All Conditions

Neoplasms

Rare Diseases

Gallbladder Diseases

Gallbladder Neoplasms

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Gallbladder Cancer

The extracted DNA from bile will be analyzed by UCAD to determine the level of CNV. And the patient will be followed more than 1 year.

The level of CNV

Copy number variation(CNV) refers to ongoing chromosome segregation errors throughout consecutive cell divisions. CNV is a hallmark of human cancer, and it is associated with poor prognosis, metastasis, and therapeutic resistance. Analyzing CNV of the DNA extracted from bile samples in gallbladder seems a promising method for diagnosing, monitoring, and predicting the prognosis of patients with gallbladder cancer. CNV can be assessed using experimental techniques such as bulk DNA sequencing, fluorescence in situ hybridization (FISH), or conventional karyotyping. However, these techniques are either time-consuming or non-specific. The investigators here intend to study whether a new method named Ultrasensitive Chromosomal Aneuploidy Detection (UCAD), which is based on low-coverage whole-genome sequencing, can be used to analyze CNV thus helping diagnose gallbladder cancer and assessing follow-up.

DNA from bile in the gallbladder will be analyzed

UCAD for Diagnosing Benign or Malignant Gallbladder Diseases and Follow-up

A Prospective, Multi-centre, Single-blinded Study of UCAD for Diagnosing Benign or Malignant Gallbladder Diseases and Follow-up

Ultrasensitive chromosomal aneuploidy detection (UCAD) uses low-coverage whole-genome sequencing technology to detect DNA chromosomal instability in samples. By detecting DNA extracted from patients' bile and blood, bioinformatics can be used to analyze the differences in CNV between benign and malignant gallbladder diseases, and a prediction model for gallbladder cancer.

Shanghai Zhongshan Hospital

Ruijin Hospital

Changhai Hospital

Shanghai Changzheng Hospital

Eastern Hepatobiliary Surgery Hospital

First Affiliated Hospital Xi'an Jiaotong University

Jiangsu Provincial People's Hospital

Third Affiliated Hospital, Sun Yat-Sen University

First Affiliated Hospital of Zhejiang University

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Second Hospital of Jilin University

West China Hospital

Southwest Hospital, China

Afﬁliated Hospital of North Sichuan Medical College

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Carcinoma

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Pre-surgery patients with urothelial carcinoma will be the experimental group to determine the sensitivity and specificity of UroCAD analysis, the result will be compared with cytology and FISH test.

Patients being treated for other diseases but without any tumor will provide a negative control to provide data for determining the sensitivity and specificity of UroCAD analysis.

The extracted DNA from morning urine will be analyzed by UroCAD to determine the level of CNV. And the patient will be followed for up to 2 years.

Shuxiong Zeng, M.D., Ph.D.

Shuxiong Zeng, M.D. Ph.D

Chuanliang Xu, M.D.,Ph.D.

Urothelial carcinoma (UC) is common malignancy and is considered to be one of the costliest cancers. The traditional diagnostic methods of UC present with some shortcomings. For example, the specificity of CTU remains low while cystoscopy is invasive and expensive. Therefore, a noninvasive diagnostic method with high accuracy is urgently needed. Our previous study has proved that UroCAD, which is able to detect chromosomal aberrations of the urine exfoliated cells, is a reliable method in diagnosing UC with sensitivity and specificity of 82.5% and 96.9%, respectively. But its potential in UC patient follow-up hasn't been assessed yet and the the accuracy of UroCAD in detecting UC still need to be further validated. The investigators here intended to investigate whether UroCAD can be used in UC patient follow-up and further validate the accuracy of UroCAD in diagnosing UC.

The traditional diagnostic methods of UC include CT urography (CTU) and cystoscopy. To access the upper urinary tract, CTU is commonly used. The sensitivity for detecting upper tract urothelial cancer with CTU has been reported to reach 89%. However, the specificity of CTU is 51% and it cannot get a biopsy sample. Other shortcomings include exposing the patient to high dose of radiation and the contrast material usage may impair the renal function. In the context of diagnosing lower urinary tract cancer, cystoscopy is the "gold standard" diagnostic procedure, which has a sensitivity of 68-83%. But it is invasive, uncomfortable and may miss flat lesions. Furthermore, due to the high recurrence rate of bladder cancer, surveillance of the disease with frequent cystoscopy make it one of the costliest cancers. Therefore, a noninvasive diagnostic method with high accuracy is urgently needed.

Copy number variations (CNVs) refers to the ongoing acquisition of genomic alterations ranging from point mutations to gross chromosomal rearrangements, is a hallmark of cancer which is found in 60-80% of human cancer, and it positively correlates with high tumor stage, poor prognosis, metastasis and therapeutic resistance. Several researches have investigated the value of detecting chromosomal instability with sWGS in either cell-free (cf)DNA or genomic DNA as a noninvasive diagnostic method for cancers and yielded quite fine results. Our previous research has also proved the UroCAD model reached performance of AUC=0.928, with sensitivity, specificity and accuracy of 82.5%, 96.9% and 89.0%, respectively. This test also showed superiority in diagnosing upper tract urothelial cancer compared with urinary cytology test.

Here the investigators intended to conduct a prospective, multicenter, single-blinded research to further validate the value of UroCAD in diagnosing UC and investigate the potential of UroCAD in UC patient follow-up by analyzing the CNV level of patient DNA extracted from urine exfoliated cells and follow UC patient for up to 2 years to determine if there is a correlation between CNV level and patient prognosis. Patient information, which is acquired every 3 months after surgery, including survival status, CNV level in urine exfoliated cells, treatment during this period, medical examination during this period, etc.

DNA from Urine Exfoliated Cells will be analyzed

A Prospective, Multi-centre, Single-blinded Study of UroCAD for Urothelial Carcinoma Diagnosis and Follow-up

We will try to protect the information of the included participants

number of patients "declared positive" with the UroCAD test among the patients suffered from urothelial carcinoma and number of patients "declared negative" with the UCAD test among the patients without cancer.

Compare the CNV level with the patient information gathered by follow-up to determine whether there is a correlation between CNV level and patient prognosis or disease progression

level of CNV in the urine sample compared with the grade of the tumor confirmed by histopathologic examination

level of CNV in the urine sample compared with the stage of the tumor confirmed by histopathologic examination

number of patients "declared positive" with the UroCAD analysis versus patients "declared positive" with the urine cytology and number of patients "declared negative" with the UroCAD analysis versus patients " declared negative " with the urine cytology

RenJi Hospital

The First Affiliated Hospital of Soochow University

Zhejiang Provincial People's Hospital

Tongji Hospital

Tianjin Medical University Second Hospital

Qilu Hospital of Shandong University

Xibei Hospital

Principal Investigator

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Pre-tissue biopsy patients with suspected prostate carcinoma will be the experimental group to determine the sensitivity and specificity of PROUD analysis, the result will be compared with histological results and PCA3 test.

Patients being treated for other diseases but without any tumor will provide a negative control to provide data for determining the sensitivity and specificity of PROUD analysis.

The extracted DNA from morning urine will be analyzed by PROUD to determine the level of CNV.

Yueqing Tang, MD

Zunlin Zhou, MD

Prostate carcinoma (PC) is common malignancy and is considered to be the highest incidence in the old males. The traditional diagnostic methods of PC present with some shortcomings. For example, the specificity of serum PSA remains low while prostate needle biopsy is invasive and false negative in some case, even causing missed diagnosis of some high risk PC, and over diagnosis of PC is not rare. Therefore, a noninvasive diagnostic method with high accuracy is urgently needed. Our previous study has proved that PROstate cancer Urine Detector (PROUD), which is able to detect chromosomal aberrations of the urine exfoliated cells, is a reliable method in diagnosing urothelial carcinoma with sensitivity and specificity of 82.5% and 96.9%, respectively. But its potential in PC diagnosis hasn't been assessed yet and the accuracy of PROUD in detecting PC need to be validated. We here intended to investigate whether PROUD can be used in PC diagnosis and further validate the accuracy of PROUD in diagnosing PC.

The traditional diagnostic methods of PC include serum PSA and prostatic biopsy (PB). To screen the PC in high risk population, PSA is commonly used. The early detection of PC is actually carried out by the association of digital rectal examination (DRE) and serum total prostate-specific antigen (tPSA) level. The usual upper limit for tPSA is 4 ng ml-1. However, between 4 and 10 ng ml-1, there exists a diagnostic grey zone with an estimated probability of only 40% of PC in men with normal findings on DRE. Prostrate cancer can only be accurately differentiated from benign prostate hyperplasia(BPH) and prostatitis by pathological proof, usually obtained by subsequent invasive PB. To refine the indications for PB, and therefore to reduce morbidity, new indicators based on tPSA were developed: age-adjusted tPSA cutoffs, tPSA velocity or tPSA density where the elevated tPSA is indexed to the gland size. The most commonly used indicator is free/total PSA ratio (f/tPSA), which may help to predict PC or BPH in its extreme values. However, the probability of PC at biopsy among men with a PSA value between 4 and 10 ng ml-1 and normal findings on DRE ranged from 56% for men with an f/tPSA ratio of \<10% to 8% for men with a ratio \>25%, underlying the lack of accuracy of the f/tPSA indicator. PB is the "gold standard" diagnostic procedure, which is invasive, uncomfortable and with possible adverse side effects as local bleeding and infectious complications including drug resistant bacterial strains. Furthermore, repeated tissue biopsy is needed in some cases for the missed diagnosis of PC, in the other hand, causing over diagnosis of the insignificant clinical PC cases.

The difficulty of estimating the risk of PC when there is a suspicious DRE without nodule, when tPSA ranges between 4 and 10 ng ml-1 or when f/tPSA has an average value (between 15 and 25%), taken together with the morbidity due to PB, highlights the need of new predictive markers for PC.

In urine samples, it is reported than whole-genome gene expression analysis, as noninvasive method, obtained from PC, BPH,and control groups by using the microarray system, showed the differences of gene expression profiles.To improve the specificity of prostate cancer diagnosis, prostate-cancer-specific markers, such as prostate cancer gene 3 (PCA3),are needed. The strong association between PCA3 mRNA overexpression and malignant transformation of prostate epithelium indicates its potential as a diagnostic biomarker. The PCA3 test of PC has a sensitivity ranged from 47%-69% and specificity from 72%-83%.

Copy number variations (CNVs) refers to the ongoing acquisition of genomic alterations ranging from point mutations to gross chromosomal rearrangements, is a hallmark of cancer which is found in 60-80% of human cancer, and it positively correlates with high tumor stage, poor prognosis, metastasis and therapeutic resistance. Several researches have investigated the value of detecting chromosomal instability with sWGS in either cell-free (cf)DNA or genomic DNA as a noninvasive diagnostic method for cancers and yielded quite fine results. Our previous research has also proved the PROUD model reached performance of AUC=0.928, with sensitivity, specificity and accuracy of 82.5%, 96.9% and 89.0%, respectively. This test also showed superiority in diagnosing upper tract urothelial carcinoma compared with urinary cytology test.

Here we intended to conduct a prospective, multicenter, single-blinded research to further validate the value of PROUD in diagnosing PC by analyzing the CNV level of patient DNA extracted from urine exfoliated cells.

A Prospective, Single-centre，Single-blinded Study of PROUD for Prostate Carcinoma Diagnosis

A Prospective, Single-centre,Single-blinded Study of PROUD for Prostate Carcinoma Diagnosis

number of patients "declared positive" with the PROUD test among the patients suffered from prostate cancer.

number of patients "declared negative" with the PROUD test among the patients without cancer.

level of CNV in the urine sample compared with the grade of the tumor confirmed by histopathologic examination.

through study completion, an average of 30 months

number of patients "declared positive" with the PROUD analysis versus patients "declared positive" with the PCA3 test.

number of patients "declared negative" with the PROUD analysis versus patients " declared negative " with the PCA3 test.

number of patients "declared positive" with the PROUD test among the patients suffered from prostate cancer in different PSA subgroup(≤4,≥10，between 4-10ng ml-1).

number of patients "declared negative" with the PROUD test among the patients without cancer in different PSA subgroup(≤4,≥10，between 4-10ng ml-1).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
UCAD for Diagnosing Benign or Malignant Gallbladder Diseases and Follow-up	NCT06232538	Gallbladder Can...	The level of CN...	18 Years -	Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
A Prospective, Multi-centre, Single-blinded Study of UroCAD for Urothelial Carcinoma Diagnosis and Follow-up	NCT04432909	Urothelial Carc...	The level of CN...	18 Years -	Changhai Hospital
A Prospective, Single-centre，Single-blinded Study of PROUD for Prostate Carcinoma Diagnosis	NCT04699344	Prostate Carcin...	The level of CN...	18 Years -	Qilu Hospital of Shandong University
UCAD for Diagnosing Benign or Malignant Gallbladder Diseases and Follow-up	NCT06232538	Gallbladder Can...	The level of CN...	18 Years -	Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
A Prospective, Single-centre，Single-blinded Study of PROUD for Prostate Carcinoma Diagnosis	NCT04699344	Prostate Carcin...	The level of CN...	18 Years -	Qilu Hospital of Shandong University

Spots Global Cancer Trial Database for the level of cnv