Analysis of Volatile Organic Compounds Released from SW480 Colorectal Cancer Cells and from the Blood of the Tumor-Bearing Mice

Abstract

Background: Volatile organic compound (VOC) analysis provides an elegant approach for colorectal cancer screening. Many studies have focused on the relationship between VOCs in exhaled breath and cancer. However, many factors can affect the presence of VOCs in exhaled breath, such as smoking and diet. An organic compound with a higher vapor pressure or volatility can be detected in the headspace of cancer cells or blood samples. Therefore, analyzing VOCs in the blood of rats inoculated with colorectal cancer tissue and in SW480 medium from cultured colorectal cancer cells provides more accurate results. Methods: After collecting venous blood from rats inoculated with cancer cells at different times, removing cancer tissue from the inoculated rats, and harvesting the medium of cancer cells cultured in the presence or absence of chemotherapy drug and of intestinal epithelial cells, we used solid phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) to analyze the headspace of the blood and media to evaluate the VOC profiles. Statistical analysis was conducted using principal component analysis (PCA) and orthogonal partial least squares(OP-LSDA). Findings: In the in vivo and in vitro analyses of the colorectal cancer samples, we found a variety of compounds, such as cyclohexanone; 1-hexanol, 2-ethyl-; butylated hydroxytoluene; cyclotrisiloxane, hexamethyl-; pentanoic acid, 2,2,4-trimethyl-3-hydroxy-isobutyl ester; and acetone. Among these compounds, butylated hydroxytoluene is unique with regard to its presence during the processes of tumor growth and resection; it is also present during the processes of tumor cell growth and necrosis. Acetone showed unique trends in the in vivo experimental group. Interpretation: By analyzing VOC fingerprints relating to CRC, we found that butylated hydroxytoluene and acetone have unique signatures that may provide the basis for clinical diagnosis and disease assessment. Funding Statement: The project is funded by the National Natural Science Foundation of China (No. 81402462); Nn10 program and Distinguished Young Scholars Fund of Harbin Medical University Cancer Hospital; The Yuweihan Fund for Distinguished Young Scholars of Harbin Medical University; Harbin Science and Technology Innovation Scholars Fund (2017RAXXJ087); Heilongjiang Province Postdoctoral Research Fund. Declaration of Interest: The authors declare no potential conflicts of interest. Ethics Approval Statement: This study’s protocol was approved by the Ethics Committee at the First Affiliated Hospital of Harbin Medical University (No.2017005).