Endothelial cell-specific molecule-1 (ESM-1) is a secretory proteoglycan comprising a mature polypeptide of 165 amino acids and a single dermatan sulfate. The aim of this study was to evaluate endothelial cell-specific molecule-1 (ESM-1) as a hepatocellular carcinoma (HCC) marker and to analyze the effect of ESM-1 gene silencing in hepatocellular carcinoma cells. RT-PCR and Western Blot analysis revealed overexpression of ESM-1 in human HCC liver tissue and in serum from patients with HCC. Sandwich ELISA assay was used for quantitative analysis of ESM-1 in serum. Levels of ESM-1 were significantly elevated in the serum of patients with HCC (n = 40) as compared to serum from patients with hepatitis (AH, n = 40; CH, n = 39) or liver cirrhosis (n = 40) or from healthy subjects (n = 40). The accuracy of ESM-1 for HCC was higher than that of α-fetoprotein (AFP) according to ROC curve analysis. Expression of ESM-1 siRNA decreased cell survival through the inhibition of NF-κB pathway and induced cell cycle arrest by PTEN induction resulting in the inhibition of cyclin D1 in SK-Hep1 cells. Furthermore, ESM-1 silencing inhibited cell migration and invasion of SK-Hep1 cells. This study demonstrates that ESM-1 as a potential tumor marker is overexpressed in most tissues and serum in the presence of HCC and is involved with cell survival, cell cycle progression, migration, and invasion of hepatocellular carcinoma cells. Based on our results, we suggest that ESM-1 or a combination of ESM-1 and AFP is useful markers for diagnosis of HCC and ESM-1 may be useful therapeutic target of hepatocellular carcinoma.
No ideal serum markers for screening colorectal cancer (CRC) have been identified. The aim of this study was to determine the usefulness of endothelial cell-specific molecule-1 (ESM-1) as a serum marker for CRC. Illumina microarray was carried out to search CRC-related biomarkers. cDNA microarray detected that ESM-1 was one of the overexpressed genes in CRC. Overexpression of ESM-1 mRNA was confirmed in tissues of CRC by RT-PCR and real-time PCR. Immunohistochemical staining showed strong expression of ESM-1 in the cytoplasm of tumor cells. Overexpression of ESM-1 in human serum with CRC was found by Western blot analysis. For quantitative analysis of ESM-1 in serum, we determined the ESM-1 levels in serum specimens using an ELISA kit. We showed that the ESM-1 levels in the serum of patients with CRC were significantly elevated (70.1 ± 29.7 pg/mL) compared to healthy subjects (29.7 ± 14.9 pg/mL). The accuracy, sensitivity, and specificity of ESM-1 for CRC were 0.94, 99%, and 73%, respectively, by receiver operating characteristics curve analysis. The positive predictive value and negative predictive value were 63% and 95%, respectively. The likelihood ratios of a positive or negative test result were 73 and 0.27, respectively. When analyzed with a Cox regression model, a higher serum ESM-1 level ( ‡76.0 pg/mL) was correlated with poor prognosis. This study suggests that expression of ESM-1 is increased in tissue and serum of CRC patients and that ESM-1 can be used as a potential serum marker for the early detection of CRC. (Cancer Sci 2010; 101: 2248-2253 C olorectal cancer is one of the most common cancers in the world. It is most effectively treated when detected at an early stage. Various methods, including the fecal occult blood test and colonoscopy, are currently used for screening CRC, and increase the rates of detection of early stage cancer. Regular colonoscopic examinations are recommended, but the high cost and invasiveness of the procedure is an obstacle to its application as a screening test for CRC. Furthermore, the sensitivity and specificity of fecal occult blood tests are low, although inexpensive and non-invasive.(1-3) Therefore, more accurate and acceptable tumor markers for the early detection of CRC are needed.Recent studies have shown that CRC can be detected by noninvasive markers, such as specific changes in serum proteins. Serum markers have the potential to greatly increase the effectiveness of CRC screening programs, as they can be analyzed relatively non-invasively, conveniently, and economically. (4)
Abstract:The East/Japan Sea (hereafter, the East Sea) is highly dynamic in its physical phenomena and biological characteristics, but it has changed substantially over the last several decades. In this study, a recent decadal trend of primary productivity in the East Sea was analyzed based on Moderate-Resolution Imaging Spectroradiometer (MODIS)-derived monthly values to detect any long-term change. The daily primary productivities averaged using monthly values from 2003 to 2012 were 719.7 mg¨C¨m´2¨d´1 (S.D.˘197.5 mg¨C¨m´2¨d´1, n = 120) and 632.3 mg¨C¨m´2¨d´1 (S.D.˘235.1 mg¨C¨m´2¨d´1, n = 120) for the southern and northern regions of the East Sea, respectively. Based on the daily productivities, the average annual primary production in the East Sea was 246.8 g¨C¨m´2¨y´1, which was substantially higher than that previously reported in deep oceans. However, a decreasing trend (13% per 10 years) in the annual primary production was observed in the East Sea within the study period from 2003 to 2012. The shallower mixed layers caused by increased temperature could be a potential cause for the decline in annual production. However, this decline could also be part of an oscillation pattern that is strongly governed by the Pacific Decadal Oscillation (PDO). A better understanding of primary productivity patterns and their subsequent effects on the marine ecosystem is required for further interdisciplinary studies in the East Sea.
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