Serum CD166: A novel hepatocellular carcinoma tumor marker
Introduction
Hepatocellular carcinoma (HCC) is a major health problem worldwide, and it is the sixth most common malignancy in the world, with more than half a million new cases annually [1]. Recently, YAP was revealed to promote HCC cell proliferation and transformation [2], [3], [4], [5], [6], [7]. YAP over-expression in HCC is significantly associated with poorer tumor differentiation [8]. In addition, clinical studies revealed that YAP was overexpressed in 62% of HCC patients, and it was an independent predictor of poor disease-free survival and overall survival in HCC [8]. These results suggest that YAP activation plays an important role in liver cancer development. However, proteins that reflect YAP function in HCC, which may be used as non-invasive diagnostic tumor markers, remain unknown. Membrane proteins are promising candidates because these proteins derive from tumor lesions, and they are easily released into the blood flow. However, HCC-specific and YAP-dependent membrane proteins have not been fully described.
Recently, we reported that membrane protein CD166 enhances YAP function to exert a carcinogenetic role in HCC, which demonstrated that CD166 is an upstream regulator of YAP. We also revealed that CD166 and YAP are closely correlated in HCC patients, which suggests an important relationship [9]. However, whether CD166 is detected in the sera of HCC patients and the use of this protein a valuable HCC tumor marker has not been identified.
Section snippets
Blood samples
All patients who were diagnosed with HCC (mean age ± SD, 54.89 ± 9.21 years; male:female ratio, 18:1), colon cancer (mean age ± SD, 63.31 ± 11.5 years; male:female ratio, 1.21:1), hepatitis B (mean age ± SD, 39.4 ± 14.5 years; male:female ratio, 1.4:1), hepatitis C (mean age ± SD, 55.7 ± 15.6 years; male:female ratio, 1.35:1), cirrhosis (mean age ± SD, 57.6 ± 14.2 years; male:female ratio, 2.73:1), gastric cancer (mean age ± SD, 54.9 ± 14.6 years; male:female ratio, 6:1), breast cancer (mean age ± SD, 49.2 ± 13.3 years; all
CD166 is highly up-regulated in HCC
We performed IHC on TMA slides that contained 24 normal liver tissue samples and 403 HCC tissue samples using an anti-CD166 antibody to investigate the up-regulation of CD166 in HCC. CD166 was highly up-regulated in HCC tissues compared to those in normal control tissue (Fig. 1). We also observed that CD166 was recruited to the cell membrane in HCC tissues, while this protein was not detected in normal liver tissues (Fig. 1). These observations suggest that membrane protein CD166 is easily
Discussion
The treatment options for liver cancer are extremely limited primarily because the pathogenetic mechanisms of this disease are not completely known. CD166 is a cell surface member of the immunoglobulin superfamily [10] that is over-expressed in several types of epithelial tumors, and it is a valuable prognostic marker of disease progression and poor survival [11], [12], [13]. Our previous study revealed that the activation of anti-apoptotic canonical NF-κB signaling greatly induced CD166
Acknowledgments
This work was wholly or partially supported by the National Natural Science Foundation of China (Grants 81201884, 81201363 and 81301689), Shanghai Committee of Science and Technology Yangfan Project (Grant 14YF1412300, to Jiayi Wang), Young College Teachers' Training Scheme of Shanghai (ZZjdyx13007, to Yongxia Qiao) and the Tongji University Outstanding Youth Training Project (1501219080, to Jiayi Wang).
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2018, Clinica Chimica ActaCitation Excerpt :In addition to its sensitivity, NRP1 also had high specificity without the interference from diseases, such as hepatitis B/C, cirrhosis, gastric, breast and lung cancer. Recently, additional membrane proteins such as DKK1, MCAM and CD166 have been reported to show better diagnostic performance than the classic HCC tumor marker AFP [37–39], further demonstrating the prospects for the membrane proteins as HCC tumor markers. Future studies should focus on the comparison of diagnostic performances for several membrane proteins or their use in combination.
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These two authors contributed equally to this study.