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Plasma Lysophosphatidylcholine Levels: Potential Biomarkers for Colorectal Cancer

Zhenwen Zhao, Yijin Xiao, Paul Elson, Haiyan Tan, Sarah J. Plummer, Michael Berk, Phyu P. Aung, Ian C. Lavery, Jean P. Achkar, Li Li, Graham Casey, Yan Xu

From the Department of Cancer Biology, Lerner Research Institute; Departments of Colorectal Surgery and Gastroenterology, Taussig Cancer Center, Cleveland Clinic; Department of Family Medicine-Research Division, Case Western Reserve University, Cleveland, OH; and the Department of Obstetrics and Gynecology, Indiana University Cancer Center, Indiana University School of Medicine, Indianapolis, IN

Address reprint requests to Yan Xu, PhD, Department of Obstetrics and Gynecology, Indiana University Cancer Center, Indiana University School of Medicine, 975 W Walnut St IB355A, Indianapolis, IN 46202; e-mail: xu2{at}iupui.edu

Purpose: Plasma levels of lysophospholipids were evaluated as potential biomarkers for colorectal cancer (CRC), where a highly reliable and minimally invasive blood test is lacking.

Patients and Methods: Patients with CRC (n = 133) and control subjects (n = 125) were recruited through the Cleveland Clinic. Preoperative plasma samples were analyzed for lysophospholipid levels using liquid chromatography mass spectrometry in a blinded fashion. Participants were randomly divided in a 2:1 ratio into a "training set" (TS) and a "validation set" (VS). Logistic regression models were used in the TS to identify markers that best discriminated between CRC and controls. A cutoff point for the final discriminating model was developed using the receiver operating characteristic curve to achieve 95% specificity. All analyses were then independently validated in the VS.

Results: Plasma levels of several lysophosphatidylcholines (LPCs), including 18:1- and 18:2-LPC, were significantly decreased in CRC patients compared with controls (P < .001). A model based on total saturated LPC and the difference between the proportional amounts of 18:2-LPC and 18:1-LPC in the unsaturated LPC fraction was derived from the TS. This model achieved a sensitivity and specificity of 82% and 93%, respectively, in the VS. Overall, 118 (94%) of 125 control subjects and 113 (85%) of 133 CRC cases were correctly identified, including eight (89%) of nine CRC cases with stage T1 disease.

Conclusion: Percentage of 18:1-LPC or 18:2-LPC plasma levels compared with total saturated LPC levels, either individually or in combination, may represent potential biomarkers for CRC.

Supported in part by a Ralph C. Wilson Sr and Ralph C. Wilson Jr Medical Research Foundation grant and a GI SPORE pilot grant from the Cancer Center of The Case Western Reserve University (Y.X.); a grant from the State of Ohio Biomedical Research and Technology Transfer Commission (G.C.).

Z.Z. and Y. Xaio contributed equally to this work.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.