RRC ID 56636
Author Piao L, Yang Z, Jin J, Ni W, Qi W, Xuan Y.
Title B7H4 is associated with stemness and cancer progression in esophageal squamous cell carcinoma.
Journal Hum Pathol
Abstract B7H4 is overexpressed in human cancers and often correlates with poor clinical outcome. There is a lack of data on the role of B7H4 as a cancer stem cell (CSC) regulator in esophageal squamous cell carcinoma (ESCC) and its expression levels compared to other stemness genes in ESCC. In this study, we have assessed the expression of B7H4 and cancer stemness proteins in 156 paraffin-embedded ESCC tissue samples using immunohistochemistry as well as in ESCC cell lines using Western blotting and immunofluorescence imaging. The correlation of B7H4 expression with clinicopathological parameters, cell cycle regulating genes, and PI3K/Akt/NF-κB signaling genes was investigated. The expression of B7H4 in ESCC tissue was correlated with the primary tumor (pT) stage, stromal activity, and the expression of CD68 and HIF-1α. However, B7H4 expression was negatively associated with CD8+ T cell infiltration in ESCC tissues. Moreover, B7H4 was found to be strongly linked to prognostic factors leading to poor clinical outcome. B7H4-expressing cancer cells also expressed known cancer stemness proteins (Sox9, LSD1, Oct4, and LGR5). Moreover, B7H4, Sox9, LSD1, Oct4, and LGR5 were highly expressed in more poorly differentiated ESCC cell lines. Notably, B7H4 expression was positively associated with the expression of cell cycle regulators such as cyclin D1, p27, and PI3K/Akt/NFκB signaling proteins. B7H4 could be a novel cancer stem cell marker for the prognostic evaluation of ESCC patients as well as a potential therapeutic target against ESCC.
Volume 80
Pages 152-162
Published 2018-10-1
DOI 10.1016/j.humpath.2018.05.021
PII S0046-8177(18)30189-8
PMID 29885401
MeSH Biomarkers, Tumor / genetics Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / pathology Cell Proliferation / genetics Esophageal Neoplasms / genetics Esophageal Neoplasms / pathology* Esophageal Squamous Cell Carcinoma / pathology* Female Gene Expression Regulation, Neoplastic* Humans Immunohistochemistry / methods Male Neoplastic Stem Cells / pathology Phosphatidylinositol 3-Kinases / genetics Prognosis V-Set Domain-Containing T-Cell Activation Inhibitor 1 / genetics*
IF 2.74
Times Cited 5
Human and Animal Cells TE-1(RCB1894) TE-8(RCB2098) TE-10(RCB2099) TE-11(RCB2100)