Abstract

Lymph node metastasis remains a key factor that affects the prognosis of patients with colon cancer. The aim of the present study was to identify and evaluate serum metabolites as biomarkers for the detection of tumor lymph node metastasis and the prediction of patient survival. The present study analyzed the metabolites in the serum of patients with advanced colon cancer both with and without lymph node metastasis. Blood samples from 104 patients with stage T3 colon cancer were collected and analyzed using liquid chromatography-mass spectrometry. The metabolites were structurally confirmed with data from the Human Metabolome Database. The association between the serum metabolites and the clinicopathological characteristics and survival time of patients from the present study was analyzed. Overall, 227 different metabolites were identified in the serum of patients with stage T3 colon cancer with or without lymph node metastasis. Furthermore, 17 of these metabolites may potentially distinguish those patients with lymph node metastasis from those patients without. In addition, five factors, including abscisic acid, calcitroic acid and glucosylsphingosine presence in the serum, age and sex, were identified as independent predictors for lymph node metastasis (P<0.05). Furthermore, three factors, including abscisic acid, calcitroic acid and glucosylsphingosine presence in the serum were independent predictors for patient survival (P<0.05). In conclusion, the serum levels of abscisic acid, calcitroic-acid and glucosylsphingosine may be considered as potential biomarkers to predict the occurrence of lymph node metastasis and the survival time of patients with colon cancer.

Highlights

  • Colon cancer has the second highest morbidity and mortality rates in the United States with 102,000 new cases andKey words: colon cancer, lymph node metastasis, serum metabolites, liquid chromatography‐mass spectrometry, prognosis51,000 deaths [1,2], accounting for >1,000,000 newly diagnosed cases and up to 500,000 cancer‐associated mortality cases estimated per year between 2016 and 2019 worldwide [3]

  • Almost all samples were separated into 2 groups in the Principal component analysis (PCA) plots, suggesting that these serum metabolites may allow the classification of patients according to their stage (Fig. 2)

  • The incidence of colon cancer has increased each year over the last decades, and this disease, which markedly alters the quality of life of patients, is associated with a high mortality rate [1,2]

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Summary

Introduction

Colon cancer has the second highest morbidity and mortality rates in the United States with 102,000 new cases and51,000 deaths [1,2], accounting for >1,000,000 newly diagnosed cases and up to 500,000 cancer‐associated mortality cases estimated per year between 2016 and 2019 worldwide [3]. Patients with early stage disease may present with no specific symptoms or clinical manifestations; once symptoms occur, the disease may have already progressed to an advanced stage [4]. This delays the opportunity to provide the patient with curative surgery, and thereby increases the risk of mortality [5]. Detection methods for colon cancer include the fecal occult blood test, the analysis of certain gastrointestinal tumor markers, such as CEA and CA19‐9, in the serum and the colonoscopy [6,7,8,9,10,11]. Further identification and evaluation of serum biomarkers could help clinicians to detect colon cancer early or predict the prognosis and treatment responses in order to successfully treat patients

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