http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Identification of glyco-biomarker candidates for lung cancer using novel glyco-technologies
Yoshitoshi Hirao,Hideki Matsuzaki,Jun Iwaki,Minako Abe,Akira Togayachi,Atsushi Kuno,Takashi Ohkura,Hiroyuki Kaji,Masaharu Nomura,Masayuki Noguchi,Yuzuru Ikehara,Hisashi Narimatsu 한국당과학회 2012 한국당과학회 학술대회 Vol.2012 No.1
Lung cancer is the leading cause of cancer death worldwide. Currently, lung cancer is classified into two major types, small-cell lung cancer carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), based on the histological appearance. The histological classification has important implications in the clinical practice guideline and the prediction of the patient prognosis. However, conventional serum markers used in clinical tests are insufficient for clinical demands due to the low sensitivity and the low specificity to distinguish them. We have identified a number of glyco-biomarker candidate molecules from lung cancer cell lines using our developed glycoproteomics technologies such as lectin microarray and LC/MS-based protein analysis. On the validation studies, we found out that the selected molecules showed characteristic lectin biding profiles depending on either SCLC or NSCLC. Therefore, combination of these glyco-biomarkers could be expected to improve the diagnostic accuracy for histological classification in lung cancer compared to protein expression alone.
Atsushi Kuno,Masaharu Nomura,Hideki Matsuzaki,Tomoko Nakagawa,Atsushi Matsuda,Yoshitoshi Hirao,Masao Sasaki,Norihiro Ikeda,Toshitaka Nagao,Yuzuru Ikehara,Hisashi Narimatsu 한국당과학회 2012 한국당과학회 학술대회 Vol.2012 No.1
Cell glycome is defined by the glyco synthesis machinery regulated by harmonized expression of more than 100 glycogenes. The machinery-dependent glycome drastically shifts during cell progression and differentiation in association with tumorigenesis and malformation, and thus it motivates us to discover the disease-related alteration in glycosylation. Glycan-targeted histochemical approaches using lectin and anti-glycogene antibodies have provided some key information to characterize specific histological types of cells in pathology. However, this approach is not suitable for the comprehensive analysis targeting the cell glycome, and thus may fail to provide insight into glycome shift during the disease progression. Several years ago, we developed the methodology for rapid and systematic glycome shift analysis targeting formalin-fixed tissue specimens by means of lectin microarray. The resultant method enabled simultaneous observation of over 40 lectins interacted with glycoproteins in 1 mm2 of the tissue specimens. Recently, we sophisticated this methodology to be suitable for comparative analysis of a series of cells in specific groups isolated from a single tissue specimen by laser microdissection, and now our research has gained interest in the variability and distribution of cell glycome in the tissue, i.e., “tissue glycome mapping”. In this meeting, we will summarize the advantage of this new methodology and its application for glyco-biomarker discovery, as well as the construction of “tissue glycome atlas”.
Verification of Wisteria floribunda agglutinin-positive glycoproteins as a cholangiocarcinoma marker
Atsushi Matsuda,Atsushi Kuno,Hideki Matsuzaki,Toru Kawamoto,Toshihide Shikanai,Yasuni Nakanuma,Masakazu Yamamoto,Nobuhiro Ohkohchi,Yuzuru Ikehara,Junichi Shoda,Jun Hirabayashi,Hisashi Narimatsu 한국당과학회 2012 한국당과학회 학술대회 Vol.2012 No.1
Cholangiocarcinoma (CC) is a lethal malignancy which exhibits asymptomatic growth infiltrating the surrounding structures, and thus,CC is usually detected at an advanced stage. The mainstay of treatment for CC is complete resection with negative surgical margins. Therefore, its diagnosis at a relatively early stage is demanded for performing the surgical resection. Since the definitive CC diagnosis relies on invasive methods such as biliary cytology and biopsy, a noninvasive assay with high diagnostic accuracy is keenly required. In the previous meeting, we reported that Wisteria floribunda agglutinin (WFA) is the best probe lectin which reliably distinguishes between CC and normal bile duct epithelia in tissue sections. Moreover, L1 cell adhesion molecule (L1CAM), CA125, and maspin were assigned as the reliable CC marker candidates by WFA-assisted glycoproteomics and immunohistochemistry. In this meeting, we will introducethe verification and validation process in one of the above candidates, L1CAM. Since the serum concentration of L1CAM was low as described in other reports (< 5 ng/mL), we firstly constructed a highly-sensitive detection system to confirm the existence of L1CAM in both bile and serum of CC patients with immunoprecipitation and western blotting. We then performed highly-sensitive glycan profiling with antibody-assisted lectin microarray (limit of detection: 25 pg) and confirmed WFA-positivity of biliary L1CAM from the CC patients. The subsequent validation study using bile samples from CC patients (n = 29) and patients with benign bile duct diseases (n = 29) showed that WFA-positive L1CAM distinguished CC from the benigndiseases with good specificity (sensitivity = 0.66, specificity = 0.93, overall accuracy = 0.79, area under the receiver operating curve [AUC] = 0.82). The combined use of the L1CAM assay with the highly-sensitive assay detecting WFA-positive sialylated mucin 1 (WFA-sialyl MUC1), a reliable CC marker (Matsuda A., et al., Hepatology, 2010), sufficiently improved the diagnostic accuracy of CC (overall accuracy = 0.84, AUC = 0.93). This combination assay using WFA–L1CAM and WFA–sialyl MUC1 will possibly be a useful serological test with enhanced reliability.