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Application of Chromosomal Instability in Early Diagnosis of Biliary Tract Carcinoma

Application of Chromosomal Instability in Early Diagnosis of Biliary Tract Carcinoma

Recruiting
18 years and older
All
Phase N/A

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Overview

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.

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

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.

Study details
    Biliary Tract Carcinoma

NCT05845554

Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University

26 January 2024

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