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Abstract
Macrophage inhibitory cytokine 1 (MIC-1/GDF15) has been characterized as a candidate biomarker for colorectal cancer (CRC) recently. However, the role of serum MIC-1 in screening patients with early stage CRC and monitoring therapeutic response have not been well-established, particularly in the combination with CEA for the screening and the prejudgment of occurrence with liver metastasis. In this study, we performed a retrospective blinded evaluation of 987 serum samples from 473 individuals with CRC, 25 with adenomatous polyps, and 489 healthy individuals using ELISA or immunoassay. The sensitivity of serum MIC-1 was 43.8% and 38.5% for CRC diagnosis and early diagnosis, respectively, which were independent of and comparatively higher than for CEA (36.6% and 27.3%) at comparable specificity. Serum MIC-1 after surgery were significantly elevated at the time of tumor recurrence, and notable increase were observed in 100% patients with liver metastasis. Besides the TNM classification and differentiation grade, MIC-1 was an independent prognostic factor contributing to overall survival. We conclude that MIC-1 can act as a candidate complementary biomarker for screening early-stage CRC by combination with CEA, and furthermore, for the first time, identify a promising prognostic indicator for monitoring recurrence with liver metastasis, to support strategies towards personalized therapy.
Highlights
Colorectal cancer (CRC) is the third most prevalent cancer and the fourth leading cause of cancer-related deaths worldwide [1]
When all patients with colorectal cancer (CRC) were subdivided according to tumor stage, the gradual increase in serum MIC-1 levels was clearly discernible (P=0.0001), with significantly higher concentrations in stage IV than in stage I–III (P
The results indicated that MIC-1 level of M1 was significantly higher than that in N1-2 and N0 group (p=0.0247, p
Summary
Colorectal cancer (CRC) is the third most prevalent cancer and the fourth leading cause of cancer-related deaths worldwide [1]. Owning to its slow development from removable precancerous lesions and curable early stages, screening for CRC in the high-risk population has the utmost potential to reduce the mortality of the disease [3]. The most reliable invasive colonoscopy, and the currently most widely used noninvasive fecal occult www.impactjournals.com/oncotarget blood test (FOBT), have inconvenience and low sensitivity limitations [4,5,6]. Blood testing for CRC screening is more compliant and acceptable [7]; no specific molecular biomarkers have been identified and validated so far that allow reliably for an accurate diagnosis of CRC. The search for novel biomarkers based on the analysis of blood samples has become a trend of current research
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