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Esophageal carcinoma and high-grade intraepithelial neoplasia patients.

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.).

Blood samples from participants in both groups were collected and methylation tests were performed according to the kit instructions.

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

Luowei Wang, MD

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.

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.

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

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.

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.

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

Spots Global Cancer Trial Database for fluorescent pcr