Abstract
BackgroundElevated expression levels of S100A6, a calcium-binding low-molecular-weight protein, were demonstrated in various malignancies. Moreover, increased serum levels of S100A6 were suggested as a novel biomarker for various inflammatory and malignant diseases including lung and gastric cancer. However, up to now, serum concentrations of S100A6 have not been analyzed in patients with cholangiocarcinoma (CCA).MethodsS100A6 mRNA expression levels were analyzed in human and murine CCA tumor samples, using semi-quantitative reverse transcriptase PCR. S100A6 serum concentrations were measured using an enzyme-linked immunosorbent assay in 112 patients with CCA referred to surgery for curative resection and were compared to those of 42 healthy controls. Results were correlated with clinical data.ResultsS100A6 mRNA expression levels were significantly up-regulated in tumor samples of CCA patients and in tumor tissue of a CCA mouse model. In contrast, serum levels of S100A6 were not significantly altered in patients with CCA compared to healthy controls. Whereas no differences became apparent within the different clinical subgroups of CCA, patients with primary sclerosing cholangitis (PSC)-based CCA displayed higher levels of S100A6 compared to the other patients. Nevertheless, patients with higher S100A6 serum concentrations showed a trend towards an impaired prognosis compared to patients with lower levels. Finally, within our cohort of patients both the diagnostic and prognostic potentials of S100A6 were similar to those of the clinically established biomarkers CEA and CA19-9.ConclusionAlthough S100A6 was expressed at significantly higher levels in human and murine CCA tumor samples, S100A6 serum levels were not regulated in patients with CCA and are thus not suitable for diagnosis of CCA. However, CCA-patients with elevated S100A6 displayed a trend toward an impaired prognosis compared to patients with lower S100A6 levels, supporting its further evaluation as a prognostic biomarker in CCA.Electronic supplementary materialThe online version of this article (doi:10.1186/s40169-016-0120-7) contains supplementary material, which is available to authorized users.
Highlights
Elevated expression levels of S100 calcium-binding protein A6 (S100A6), a calcium-binding low-molecular-weight protein, were demonstrated in various malignancies
S100A6 expression is up‐regulated in tumor tissue of human and murine CCA To confirm the recently suggested overexpression of S100A6 mRNA in tumor samples of patients with intrahepatic CCA, we analyzed tumor S100A6 mRNA levels in a cohort of patients with histologically confirmed CCA (n = 8) by using semi-quantitative reverse transcriptase PCR (qPCR) and compared them to healthy controls (n = 4)
In accordance to the existing literature, this analysis revealed significantly elevated S100A6 expression levels in tissue samples of CCA patients (Fig. 1a). To further confirm this finding, we examined S100A6 mRNA expression levels in a recently published CCA mouse model
Summary
Elevated expression levels of S100A6, a calcium-binding low-molecular-weight protein, were demonstrated in various malignancies. Increased serum levels of S100A6 were suggested as a novel biomarker for various inflammatory and malignant diseases including lung and gastric cancer. Up to now, serum concentrations of S100A6 have not been analyzed in patients with cholangiocarcinoma (CCA). Cholangiocarcinoma (CCA) accounts for 10–15 % of all hepatobiliary malignancies and is the second most common primary tumor of the liver [1]. The 5-year survival rate has remained below 5 % [14, 15], highlighting the urgent need for biomarkers allowing an early diagnosis and prognosis of the disease. As cholangiocarcinoma can be considered one of the less common types of cancer, there are only a limited number of studies evaluating potential biomarkers for CCA. No serum based marker detecting CCA with an appropriate sensitivity and specificity at early stages of disease could be established
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