Clinical trial NCT05845554: Application of Chromosomal Instability in Early Diagnosis of Biliary Tract Carcinoma
Official title: Application of Chromosomal Instability and Metagenomic Detection in Early Diagnosis of Biliary Tract Carcinoma in Bile
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Biliary Tract Carcinoma
Keywords: Biliary Tract Carcinoma
chromosomal instability
Lead sponsor: Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
Sponsor class: OTHER
Collaborators: name: Taizhou First People's Hospital
name: First Affiliated Hospital of Wenzhou Medical University
name: Sir Run Run Shaw Hospital
First posted: 2023-05-06
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with biliary tract carcinoma or participants in control group in Taizhou Hospital of Zhejiang Province, Taizhou First People's Hospital, The First Affiliated Hospital of Wenzhou Medical University and Sir Run Run Shaw Hospital from Apr 2023 until the end of this study.

Brief summary: Chromosomal instability (CIN) refers to ongoing chromosome segregation errors throughout consecutive cell divisions. CIN is a hallmark of human cancer, and it is associated with poor prognosis, metastasis, and therapeutic resistance. Analyzing CIN of the DNA extracted from cast-off cells in bile samples seems a promising method for diagnosing, monitoring, and predicting the prognosis of biliary tract carcinoma patients. CIN 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 Bile Ultrasensitive Chromosomal Aneuploidy Detection (BileCAD), which is based on low-coverage whole-genome sequencing, can be used to analyze CIN and microbial infection analysis thus help diagnosing and treating biliary tract carcinoma patients.

Detailed description: Biliary tract carcinoma account for about 3% of all digestive system tumors, with potential high metastasis and invasion ability. Their early clinical symptoms lack specificity, and they are often found in late stage with poor prognosis. CIN results from errors in chromosome segregation during mitosis, leading to structural and numerical chromosomal abnormalities. It will generate genomic heterogeneity that acts as a substrate for natural selection. Furthermore, it is proved that tumors with aneuploidies and polyploidy resulting from whole-genome doubling are related with metastasis, treatment resistance, and decreased overall survival. It is estimated that 60%-80% of human tumors exhibit chromosomal abnormalities suggestive of CIN. CIN positively correlates with tumor stage and is enriched in relapsed as well as metastatic tumor specimens. Due to the ubiquity of CIN in cancer cells, it is a potentially way to detect CIN in the cast-off cells from the bile samples for diagnosing and monitoring biliary tract carcinoma patients. BileCAD is a new method to detecting CIN in the DNA sample from patients, including extracting DNA from bile, analyzing DNA by low-coverage whole-genome sequencing, processing the data by bio-information techniques, and finally optimizing the management of biliary tract carcinoma patients.The investigators intended to conduct a prospective study by analyzing bile samples from gallbladder cancers and cholangiocarcinoma patients and control groups that without any tumor in the Bile duct and gallbladder or other organs to compare the specificity and sensitivity of BileCAD test for diagnosing biliary tract carcinoma to other modalities, such as pathological diagnosis. At the same time, the consistency of BileCAD microbial analysis results and clinical microbial culture results was compared, so as to provide more reference for clinical diagnosis.

Eligibility criteria: Inclusion Criteria:

* No systemic therapy or biliary tract surgery before the trial.
* Gallstones, bile duct space, obstructive jaundice and other suspected patients with biliary tract carcinoma.
* Male or female patients aged \>= 18 years.
* Participants signed informed consent form.

Exclusion Criteria:

* Age under 18 years.
* Individuals unwilling to sign the consent form or unwilling to provide the medical record.
* Individuals unwilling to participate in this trial.
* Individuals has any active autoimmune disease or history of autoimmune disease.
* Individuals have cardiac clinical symptoms or diseases that are not well controlled.
* Individuals have uncontrolled severe cerebrovascular, pulmonary and other diseases.

Primary outcomes:
measure: Sensitivity of bile sample analysis by BileCADanalysis
timeFrame: 12 months
measure: Specificity of bile sample analysis by BileCADanalysis
timeFrame: 12 months
Secondary outcomes:
measure: BileCAD microbial analysis results
timeFrame: 12 months
measure: BileCAD analyzed the sensitivity of different types and locations of malignant tumors
timeFrame: 12 months
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, School of Medicine，Zhejiang University
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou First People's Hospital
state: Zhejiang
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
city: Wenzhou
country: China
facility: First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
name: fabiao zhang
role: PRINCIPAL_INVESTIGATOR
affiliation: First Affiliated Hospital of Wenzhou Medical University
name: yunfeng shan
role: PRINCIPAL_INVESTIGATOR
affiliation: Taizhou First People's Hospital
name: ning mu
role: PRINCIPAL_INVESTIGATOR
affiliation: Sir Run Run Shaw Hospital
name: xiao liang
role: PRINCIPAL_INVESTIGATOR
References:
citation: Richardson TE, Walker JM, Abdullah KG, McBrayer SK, Viapiano MS, Mussa ZM, Tsankova NM, Snuderl M, Hatanpaa KJ. Chromosomal instability in adult-type diffuse gliomas. Acta Neuropathol Commun. 2022 Aug 17;10(1):115. doi: 10.1186/s40478-022-01420-w.
citation: Al-Rawi DH, Bakhoum SF. Chromosomal instability as a source of genomic plasticity. Curr Opin Genet Dev. 2022 Jun;74:101913. doi: 10.1016/j.gde.2022.101913. Epub 2022 May 5.
citation: Bach DH, Zhang W, Sood AK. Chromosomal Instability in Tumor Initiation and Development. Cancer Res. 2019 Aug 15;79(16):3995-4002. doi: 10.1158/0008-5472.CAN-18-3235. Epub 2019 Jul 26.
citation: Liu Y, Yeh MM. Bile duct dysplasia and associated invasive carcinoma: clinicopathological features, diagnosis, and practical challenges. Hum Pathol. 2023 Feb;132:158-168. doi: 10.1016/j.humpath.2022.06.012. Epub 2022 Jun 14.
citation: Onoyama T, Matsumoto K, Koda H, Yamashita T, Kurumi H, Kawata S, Takeda Y, Harada K, Yashima K, Isomoto H. Diagnostic usefulness of KL-6 concentration of bile in biliary tract cancer. Mol Clin Oncol. 2018 Apr;8(4):561-566. doi: 10.3892/mco.2018.1571. Epub 2018 Feb 12.