Novel Blood-based Colorectal Cancer Screening Method Using Natural Killer Cell Activity and Gene Panel Expression

Natural killer cells (NK cells) are cytotoxic lymphocytes that play an important role in the innate immune system. In particular, it plays a very important defense function against host cells or cancer cells infected with a specific virus. Recent studies have shown that the activity of NK cells is decreased in patients with various carcinomas compared with normal controls, suggesting that the measurement of activity of NK cells in the blood may be helpful in the early diagnosis of cancer. In a recent study analyzing NK cell activity in 762 patients undergoing colonoscopy, NK cell activity showed performance in diagnosing advanced colorectal adenoma and colorectal cancer with sensitivities 42.2% and 85.7%, and specificity 58.3% and 59.5%, respectively. This finding suggests that NK cell activity may be useful as a screening method for colorectal neoplasms. However, as a single test, this diagnostic power is relatively low. On the other hands, another blood-based colorectal cancer screening test that using 29 gene panels algorithm has recently been reported. According to this study, 29 gene panel algorithms (Colox®) showed performance in diagnosing advanced colorectal adenoma and colorectal cancer with sensitivity of 55.4% and 79.5% and specificity of both 90.0%, respectively. for diagnosis of advanced adenoma and colorectal cancer, respectively. Although the Colox® test seems to be useful for the colorectal cancer screening using blood test, this diagnostic power is relatively low. In order to overcome low diagnostic performance of aforementioned tests (NK activity and Colox®) as a single use, combination of individual biomarkers can be a promising alternative. In this regards, the aim of this study was to evaluate the diagnostic value for predicting advanced colorectal neoplasms by combining Colox® and NK cell activity indicators.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer; Colorectal Adenoma
• Intervention / Treatment: Other: blood sampling

• Study Type: Observational
• Enrollment (Anticipated): 964

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Recruiting
    • Department of Internal Medicine, Yonsei University College of Medicine
    • Contact: TAE IL KIM, MD; Phone Number: 82-2-2228-1965; Email: taeilkim@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

1. Normal group: patients with negative colonoscopy findings (n= 238).
2. Low risk adenoma group: patients having at least one low risk adenoma (n=250).
3. High-risk adenoma group: patients having at least one of following criteria (more thatn 1 cm in size, villous or tubulovillous histologic type, high-grade dysplasia findings) (n=316).
4. Colon cancer: histologically confirmed colon cancer patients (n=160).

Description

Inclusion Criteria:

• Adults population over 40 years of age
• Patients who understood this study process and agreed to participation of this study
• Colon cancer patients who have been confirmed as colorectal cancer by endoscopic biopsy within 1 month
• Colon cancer patients who received no anticancer treatment such as surgery, chemotherapy, radiation therapy after cancer diagnosis.
• Colorectal adenoma and normal control group: Patients undergoing colonoscopy for diagnostic purposes or colorectal cancer screening.

Exclusion Criteria:

• Patients who did not agree to participate in the study and did not write their informed consent
• Vulnerable subjects with mental retardation or severe psychiatric illness.
• Patients who are not appropriate enrollment of this study by researchers judgement.
• Patients who have had an immunosuppressive drug within 6 months.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Normal group; Normal group(control group): patients with negative colonoscopy findings (n= 238).	Other: blood sampling; NK activity and gene panel expression analysis based on blood test (5cc blood sampling)
Low risk adenoma group; Low risk adenoma group: patients having at least one low risk adenoma (n=250).	Other: blood sampling; NK activity and gene panel expression analysis based on blood test (5cc blood sampling)
High-risk adenoma group; High-risk adenoma group: patients having at least one of following criteria (more than 1 cm in size, villous or tubulovillous histologic type, high-grade dysplasia findings) (n=316).	Other: blood sampling; NK activity and gene panel expression analysis based on blood test (5cc blood sampling)
Colon cancer; Colon cancer: histologically confirmed colon cancer patients (n=160).	Other: blood sampling; NK activity and gene panel expression analysis based on blood test (5cc blood sampling)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic Power for prediction of advanced colorectal neoplasms	Diagnostic Power for prediction of advanced colorectal neoplasms using combination of conventional Colox® and NK Cell Activity Indicators.	2 months

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Anticipated): June 1, 2019
• Study Completion (Anticipated): August 1, 2019

Study Registration Dates

• First Submitted: September 18, 2017
• First Submitted That Met QC Criteria: September 18, 2017
• First Posted (Actual): September 21, 2017

Study Record Updates

• Last Update Posted (Actual): January 15, 2019
• Last Update Submitted That Met QC Criteria: January 13, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Adenoma
• Other Study ID Numbers: 4-2017-0148

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No