KCNA3 and OTOP2 Gene Methylation Combined Detection Kit (Fluorescent PCR Method)

February 8, 2024 updated by: Wuhan Ammunition Life-tech Co., Ltd

Methylation Detection of KCNA3 and OTOP2 Genes in Plasma for the Auxiliary Diagnosis of Esophageal Cancer/Precancerous Lesions: a Clinical Trial

The goal of this observational study is to test the clinical efficacy of "KCNA3 and OTOP2 gene methylation combined detection kit (fluorescence PCR method)"in esophageal cancer and high-grade esophageal neoplasia auxiliary diagnosis.The main questions it aims to answer are:

  1. How consistent are the test results of the kit with the clinical reference diagnostic criteria?
  2. Sanger sequencing can visually show whether each sample contains methylation sites, so in this clinical trial, the kit results were compared with Sanger sequencing results to analyze the reagent's accuracy in detecting KCNA3 and OTOP2 gene methylation.

Each participant is required to provide no less than 10 ml of blood to complete the kit test.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Esophageal carcinoma is caused by abnormal hyperplasia of the squamous or glandular epithelium, the main pathological types are squamous cell carcinoma and adenocarcinoma. Globally, esophageal cancer has the seventh highest incidence and the sixth leading cause of cancer death. Statistics showed that in 2020, there were 604,000 new cases of esophageal cancer and 54.4 deaths.

The 5-year survival rates were significantly different in esophageal carcinomas of different stages, for example, it's 84.9% for stage Ia, 70.9% for stage Ib, 56.2% for stage IIa, 43.3% for stage IIb, 37.9% for stage IIIa, 23.3% for stage IIIb, 12.9% for stage IIIc and 3.4% for stage IV. Therefore, early diagnosis and treatment is most effective strategy to reduce the incidence and mortality of esophageal cancer.

Endoscopy and pathological biopsy are currently the "golden standard" for diagnosing esophageal cancer, however, limited by medical resources, tolerance and other issues, population screening by endoscopy is not cost-effective and applicable. There is no recognized and effective serologic marker for the detection of early esophageal carcinoma and precancerous lesions, the effect of multiple serological markers combined detection is better than that of single markers, and the accuracy were 74%~85% , but it is still suboptimal.

Methylation of the tumor suppressor gene promoter region CpG island is the most common change during tumorgenesis, studies showed that methylation events could occur at the early stages of esophageal cancer.

Circulating tumor DNA (ctDNA) is derived from DNA fragments produced by apoptosis, necrosis or secretion of tumor cells, which is a part of circulating free (cfDNA). CtDNA contains the same gene defects as its source tumor DNA, such as point mutation, rearrangement, amplification, microsatellite change, epigenetic modification, etc.

KCNA3 is a member of the protein family that encodes potassium channels and mainly affects cell viscosity. OTOP2 is a member of the protein family encoding proton transport channels, some studies have shown that the methylation levels of two genes in esophageal cancer tissues were significantly higher than that in adjacent tissues, and they can be used as a potential marker for the diagnosis of esophageal cancer.

This kit is based on real-time fluorescence PCR technology to achieve the qualitative detection of KCNA3 and OTOP2 methylation in plasma samples. Before PCR amplification, cfDNA was transformed by bisulfite and ACTB (β-Actin) gene is used us the internal reference.

Study Type

Observational

Enrollment (Actual)

1116

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Shanghai, China
        • The First Affiliated Hospital of Naval Military Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

  1. Esophageal cancer patients, number ≥ 300, containing different TNM stages.
  2. Esophageal high-grade intraepithelial neoplasis patients, number ≥70.
  3. Patients with benign diseases of digestive system including esophagitis, gastritis, enteritis, appendicitis, gastric polyps, colorectal polyps, etc. , number ≥200.
  4. Patients with other digestive system malignancies (including gastric cancer, colorectal cancer, liver cancer, pancreatic cancer, bile duct cancer, etc.) and patients with non-digestive system malignancies (including thyroid cancer, lung squamous cell carcinoma, cervical cancer, endometrial cancer, breast cancer, prostate cancer, etc.)， number ≥350.
  5. All the enrolled participants should be ≥1000.

Description

Inclusion Criteria:

  1. esophageal carcinoma patients confirmed or highly suspected by endoscopy, imaging examination or pathological biopsy, and high-grade intraepithelial neoplasia of the esophagus patients mainly enrolled from individuals who planned to undergo radical esophagectomy of esophageal cancer, endoscopic submucosal dissection or primary chemoradiotherapy.
  2. patients with benign diseases of digestive system who have undergone endoscopy (including esophagitis, gastritis, enteritis, appendicitis, gastric polyps, colorectal polyps, etc.).
  3. Untreated patients with other digestive system malignancies (including gastric cancer, colorectal cancer, liver cancer, pancreatic cancer, bile duct cancer, etc.) and patients with non-digestive system malignancies (including thyroid cancer, lung squamous cell carcinoma, cervical cancer, endometrial cancer, breast cancer, prostate cancer, etc.) confirmed by clinical reference diagnostic criteria.

Exclusion Criteria:

  1. patients who have received anti-tumor therapy such as radiotherapy/chemotherapy;
  2. Esophageal carcinoma and high-grade intraepithelial neoplasia patients who were also suffering from other malignant tumors;
  3. Samples not kept as required or samples of hemolysis;
  4. The sample volume fails to meet the detection requirements;
  5. Esophageal carcinoma patients with distant metastasis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Positive group
Esophageal carcinoma and high-grade intraepithelial neoplasia patients.
Diagnostic test: KCNA3 and OTOP2 Gene Methylation Combined Detection Kit (Fluorescent PCR Method)
Blood samples from participants in both groups were collected and methylation tests were performed according to the kit instructions.
Negative group
Patients with other digestive malignancies (including gastric cancer, colorectal cancer, liver cancer, pancreatic cancer,Cholangiocarcinoma, etc.) and patients with non-digestive malignant tumors (including thyroid cancer, lung squamous cell carcinoma, cervix Cancer, endometrial cancer, breast cancer, prostate cancer, etc.), Patients with benign digestive disorders (including esophagitis, gastritis, enteritis, appendicitis, gastric polyps, colorectal polyps, etc.).
Diagnostic test: KCNA3 and OTOP2 Gene Methylation Combined Detection Kit (Fluorescent PCR Method)
Blood samples from participants in both groups were collected and methylation tests were performed according to the kit instructions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
validity
Time Frame: Immediately after the procedure
In this study, validity indicates the consistency of methylation test with the golden diagnostic standards, including sensitivity and specificity. Sensitivity indicates the proportion of methylation-positive samples in esophageal cancer/high-grade neoplasia samples. Specificity indicates the proportion of methylation-negative samples in non-esophageal cancer/high-grade neoplasia.
Immediately after the procedure

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
reliability
Time Frame: Immediately after the procedure
In this study, the reliability evaluation included two indicators, namely the agreement rate of methylation detection with Sanger sequencing, and the Kappa value of the two methods
Immediately after the procedure

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wuhan Ammunition Life-tech Co., Ltd

Collaborators

Changhai Hospital

Investigators

  • Principal Investigator: Luowei Wang, MD, Changhai Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 28, 2022

Primary Completion (Actual)

August 30, 2023

Study Completion (Actual)

October 31, 2023

Study Registration Dates

First Submitted

December 8, 2022

First Submitted That Met QC Criteria

December 25, 2022

First Posted (Actual)

January 11, 2023

Study Record Updates

Last Update Posted (Actual)

February 13, 2024

Last Update Submitted That Met QC Criteria

February 8, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AD10

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Confidential information of the individual participant will be retained by investigators and clinical trial institutions, any personal information of subjects will not be disclosed in reports, publications, etc.

Direct access to source data and and files is only allowed for the purpose of monitoring, auditing or inspection, without revealing the subject's privacy.

The medical products administration may inspect the basic documents of clinical trials of medical devices in order to confirm the authenticity and the integrity of the collected data.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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