Abstract

In developed countries, the number of patients with colorectal cancer has been increasing, and colorectal cancer is one of the most common causes of cancer death. To improve the quality of life of colorectal cancer patients, it is necessary to establish novel screening methods that would allow early detection of colorectal cancer. We performed metabolome analysis of a plasma sample set from 282 stage 0/I/II colorectal cancer patients and 291 healthy volunteers using gas chromatography/triple-quadrupole mass spectrometry in an attempt to identify metabolite biomarkers of stage 0/I/II colorectal cancer. The colorectal cancer patients included patients with stage 0 (N=79), I (N=80), and II (N=123) in whom invasion and metastasis were absent. Our analytical system detected 64 metabolites in the plasma samples, and the levels of 29 metabolites differed significantly (Bonferroni-corrected p=0.000781) between the patients and healthy volunteers. Based on these results, a multiple logistic regression analysis of various metabolite biomarkers was carried out, and a stage 0/I/II colorectal cancer prediction model was established. The area under the curve, sensitivity, and specificity values of this model for detecting stage 0/I/II colorectal cancer were 0.996, 99.3%, and 93.8%, respectively. The model's sensitivity and specificity values for each disease stage were >90%, and surprisingly, its sensitivity for stage 0, specificity for stage 0, and sensitivity for stage II disease were all 100%. Our predictive model can aid early detection of colorectal cancer and has potential as a novel screening test for cases of colorectal cancer that do not involve lymph node or distant metastasis.

Highlights

  • In developed countries, colorectal cancer is one of the most common causes of cancer death [1], and it is treated using a combination of colonoscopy, surgery, chemotherapy, and radiotherapy

  • The aim of the present study is to find metabolite biomarker candidates that would allow the detection of cases of colorectal cancer that do not involve lymph node or distant metastasis

  • The sample set examined in this study was obtained from 282 colorectal cancer patients and 291 healthy volunteers, and the colorectal cancer patients included clinical stage 0 (N=79), I (N=80), and II (N=123) patients who were free from invasion and metastasis

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Summary

Introduction

Colorectal cancer is one of the most common causes of cancer death [1], and it is treated using a combination of colonoscopy, surgery, chemotherapy, and radiotherapy. Novel methods that would allow the early detection and diagnosis of colorectal cancer are desired in the medical field. The fecal occult blood test (FOBT) and blood tests for tumor markers are commonly used as screening methods for diagnosing colorectal cancer. The FOBT is a non-invasive and inexpensive method, but has low sensitivity and specificity for cases of colorectal cancer that do not involve lymph node or distant metastasis. As for blood tests for tumor markers, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) can be used to test for colorectal cancer, but such blood tests have low sensitivity so they are not appropriate for detecting colorectal cancer early. Colonoscopy is a more accurate and reliable method for detecting colorectal cancer early, but it cannot be used for screening because it is more invasive and expensive than blood testing. Combinations of conventional screening methods are used to detect colorectal cancer, but such combined approaches only detect about 40% of colorectal cancer cases [2].it is necessary to establish the novel screening methods for early detection of colorectal cancer with high sensitivity, high specificity, noninvasive and easy procedure

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