title: Expression of endothelial cell-specific molecule-1 regulated by hypoxia inducible factor-1α in human colon carcinoma: impact of ESM-1 on prognosis and its correlation with clinicopathological features.
abstract: Based on a previous finding that endothelial cell-specific molecule-1 (ESM-1)             is a potential serum marker for colorectal cancer (CRC), the aim of this study             was to clarify the clinicopathological significance of ESM-1 expression in CRC,             and to explore the correlation between ESM-1 and HIF-1α in the tumorigenesis of             CRC related to hypoxic conditions. ESM-1 mRNA expression was examined in CRC and             corresponding normal mucosal tissues by reverse transcriptase-polymerase chain             reaction (RT-PCR) and real-time RT-PCR. This experiment confirmed that ESM-1 levels             were high in CRC. We screened the tissue samples of 143 CRC patients. By immunohistochemistry,             we determined that the ESM-1 immunoreactivity was significantly correlated with             the tumor size, depth of invasion, nodal status, distant metastasis and Dukes'             stage, and was an independent prognostic factor for disease recurrence and worse             survival outcome (P=0.001). The modulation of ESM-1 under hypoxia was investigated,             and it was confirmed that ESM-1 expression was induced by HIF1-α and significantly             attenuated by small interfering RNA (siRNA) targeting HIF-1α in CRC cells. These             results showed that ESM-1 is significantly overexpressed, which is regulated by             HIF-1α in CRC patients, and can be used as a potential biomarker and a therapeutic             target for CRC.
authors.affiliation: Department of Pathology, Eulji University School of Medicine,                     Daejeon 301‑070, Republic of Korea.
authors.forename: Joo Heon
authors.initials: JH
authors.lastname: Kim
authors.forename: Mee Young
authors.initials: MY
authors.lastname: Park
authors.forename: Chang Nam
authors.initials: CN
authors.lastname: Kim
authors.forename: Kyo Hyun
authors.initials: KH
authors.lastname: Kim
authors.forename: Ho Bum
authors.initials: HB
authors.lastname: Kang
authors.forename: Kwang Dong
authors.initials: KD
authors.lastname: Kim
authors.forename: Jae Wha
authors.initials: JW
authors.lastname: Kim
mesh_terms: D014408:Biomarkers, Tumor; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local; D011509:Proteoglycans / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering
chemical_list: D014408:Biomarkers, Tumor; C101134:ESM1 protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D034741:RNA, Small Interfering