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Circulating exosomal CPNE3 as a diagnostic and prognostic biomarker for colorectal cancer
Authors:Bo Sun  Yiming Li  Yiming Zhou  Tien Khee Ng  Chao Zhao  Qiaoqiang Gan  Xiaodong Gu  Jianbin Xiang
Institution:1. Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China;2. Department of Ultrasound, Huashan Hospital, Fudan University, Shanghai, China

Sun, Li and Zhou have contributed equally to this work.;3. Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China

Sun, Li and Zhou have contributed equally to this work.;4. Photonics Laboratory, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia;5. Department of Electrical Engineering, The State University of New York at Buffalo, Buffalo, New York

Abstract:Exosomal proteins are emerging as relevant diagnostic and prognostic biomarkers for cancer. This study was aimed at illustrating the clinical significance of exosomal Copine III (CPNE3) purified from the plasma of colorectal cancer (CRC) patients. The CPNE3 expression levels in CRC tissues were analyzed by real-time PCR, western blot, and immunohistochemistry. Plasma exosomes were isolated to examine the CPNE3 level using ELISA. Pearson’s correlation analysis was performed to investigate the CPNE3 levels between CRC tissues and matched plasma samples. Receiver operating characteristic curve analysis was developed to measure the diagnostic performance of exosomal CPNE3. The Kaplan–Meier method and Cox's proportional hazards model were utilized to determine statistical differences in survival times. CPNE3 showed increased expressions in the CRC tissues. A moderately significant correlation was found between CPNE3 expression in CRC tissues by immunohistochemistry and matched serum exosomal CPNE3 expression by ELISA (r = 0.645,(r = 0.645, p < 0.001). < 0.001). Exosomal CPNE3 yielded a sensitivity of 67.5% and a specificity of 84.4% in CRC at the cutoff value of 0.143 pg per 1ug1 ug exosome. Combined data from carcinoembryonic antigen and exosomal CPNE3 achieved 84.8% sensitivity and 81.2% specificity as a diagnostic tool. CRC patients with lower exosomal CPNE3 levels had substantially better disease-free survival (hazard ratio HR], 2.9; 95% confidence interval CI]: 1.3–6.4; p = 0.009) = 0.009) and overall survival (HR, 3.4; 95% CI: 1.2–9.9; p = 0.026) = 0.026) compared with those with higher exosomal CPNE3 levels. Exosomal CPNE3 show potential implications in CRC diagnosis and prognosis.
Keywords:biomarker  colorectal cancer (CRC)  Copine III (CPNE3)  exosome
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