title: Down-Regulation of Nogo-B Expression as a Newly Identified Feature of Intrahepatic Cholangiocarcinoma.
abstract: Nogo-B, located in the endoplasmic reticulum, is an isoform belonging to the reticulon protein family, which is expressed specifically in cholangiocytes and non-parenchymal cells in the liver. Nogo-B expression is down-regulated with the progression of liver fibrosis, but its distinct function in liver malignancies has not been fully clarified. We have hypothesized that Nogo-B expression may be altered in intrahepatic cholangiocarcinoma (ICC), a relatively rare type of primary liver cancer with highly malignant behavior. The present study aimed to investigate the relationship between Nogo-B expression, assessed by immunohistochemical staining, and clinicopathological factors and prognosis in 34 ICC patients. Positive expression was observed in 19 (56%) of 34 ICC specimens: 6 patients (18%) with positivity levels of 1+ (positive cells in 10-50% of cancer cells) and 13 patients (38%) with 2+ (positive cells over 50%). Importantly, the remaining 15 patients (44%) were categorized as negative expression (Nogo-B-positive cells, less than 10%). Conversely, the mass-forming type of ICC tended to express Nogo-B with the degree of 2+ positivity, compared to the periductal infiltration type (p = 0.064), and the mass-forming type showed a better 5-year survival rate (66% vs. 5%) after hepatectomy (p < 0.05). However, the degree of positivity was not associated with tumor relapse rate, disease-free and overall survival, although each of the periductal infiltration type, intrahepatic metastasis, larger tumor size, and lower microvessel counts was associated with lower survival rates. We propose that Nogo-B expression is down-regulated in ICC, the implication of which, however, remains to be investigated.
authors.affiliation: Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nanashima
authors.forename: Go
authors.initials: G
authors.lastname: Hatachi
authors.forename: Tetsurou
authors.initials: T
authors.lastname: Tominaga
authors.forename: Goushi
authors.initials: G
authors.lastname: Murakami
authors.forename: Katsunori
authors.initials: K
authors.lastname: Takagi
authors.forename: Junichi
authors.initials: J
authors.lastname: Arai
authors.forename: Hideo
authors.initials: H
authors.lastname: Wada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagayasu
authors.forename: Yorihisa
authors.initials: Y
authors.lastname: Sumida
mesh_terms: D000368:Aged; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D009185:Myelin Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D000070798:Nogo Proteins; D011379:Prognosis; D015996:Survival Rate
chemical_list: D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human