Serum Midkine is a clinical significant biomarker for colorectal cancer and associated with poor survival

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Abstract
Colorectal carcinoma (CRC) is one of the most common carcinomas worldwide. Early detection is crucial for reducing morbidity and mortality. Several promising studies described the use of midkine (MK) as a tumor marker. This study aimed to investigate a larger collective to ascertain if the preoperative serum midkine level (S‐MK) is suitable as a marker for screening and if S‐MK correlates with tumor progression and localization. It was also investigated for the first time whether patients with high S‐MK show poor survival. This prospective single‐center study included 299 patients with CRC. The preoperative serum midkine level (S‐MK) was determined using ELISA. Established tumor markers Carcinoembryonic antigen (CEA) and Carbohydrate antigen 19‐9 (CA 19‐9) were collected for comparison. The median follow‐up period was 65 months. S‐MK was significantly elevated in patients with CRC (P < .001). The receiver operation characteristic (ROC) curve has an area under the curve (AUC) of 0.868 (P < .001). A cut‐off value of 56.42 pg/mL results in a sensitivity of 84.3% and a specificity of 75.4%. In the one‐way analysis of variance (ANOVA), there were no significant correlations between S‐MK and tumor progression, localization. Furthermore, no significant correlation to CEA und CA 19‐9 could be found. Kaplan‐Meier survival analysis was able to show for the first time that patients with S‐MK of more than 225 pg/mL have a significantly shorter survival. Multivariate Cox regression showed that only CEA was an independent prognostic factor for survival. S‐MK helps estimate the prognosis for CRC and is a valuable component for developing a multimarker panel for screening and surveillance.

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