title: Peritumoral activated hepatic stellate cells predict poor clinical outcome in hepatocellular carcinoma after curative resection.
abstract: The inflammatory components of the liver remnant after hepatocellular carcinoma (HCC) resection are of prognostic importance. We evaluated prognostic potential of peritumoral activated hepatic stellate cells (HSCs) in 130 HCC cases. The messenger RNA (mRNA) levels of the functional genes in HSCs (ie, seprase, osteonectin, and tenascin-C), quantitated by real-time quantitative polymerase chain reaction, and the density of peritumoral Foxp3+ T-regulatory cells (Tregs) and CD68+ macrophages (MPhi), assessed immunohistochemically in tissue microarray sections, were positively correlated with the density of peritumoral activated HSCs. The density (P= .007 for recurrence-free survival [RFS] and P=.021 for overall survival [OS]) and functional genes (seprase, P= .001 for RFS; osteonectin, P= .007 for RFS and P=.021 for OS) of peritumoral activated HSCs independently contributed to high recurrence or death rates, as did peritumoral Tregs or MPhi. Moreover, peritumoral HSCs were related to more early recurrences. It is important to note that the density of peritumoral activated HSCs, in combination with seprase and osteonectin mRNA or density of Tregs and MPhi, might predict prognoses more effectively.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School of Fudan University, Key Laboratory for Carcinogenesis and Cancer Invasion, Chinese Ministry of Education, Shanghai, Peoples Republic of China.
authors.forename: Min-Jie
authors.initials: MJ
authors.lastname: Ju
authors.forename: Shuang-Jian
authors.initials: SJ
authors.lastname: Qiu
authors.forename: Jia
authors.initials: J
authors.lastname: Fan
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Xiao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gao
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Li
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
mesh_terms: D000328:Adult; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D010450:Endopeptidases; D005260:Female; D018093:Gelatinases; D015870:Gene Expression; D006498:Hepatectomy; D055166:Hepatic Stellate Cells / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D015676:Osteonectin / Q000096:biosynthesis; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000096:biosynthesis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D010450:Endopeptidases; D018093:Gelatinases; D008565:Membrane Proteins; D015676:Osteonectin; D012333:RNA, Messenger; D012697:Serine Endopeptidases; D000099167:Fibroblast Activation Protein Alpha