title: B7-H4 expression associates with cancer progression and predicts patient's survival in human esophageal squamous cell carcinoma.
abstract: A retrospective cohort study including 112 patients suffering from esophageal squamous cell carcinoma (ESCC) was performed to investigate the expression of B7-H4 in ESCC and determine its association with patient's clinicopathological parameters and survival. Expression levels of B7-H4 on tumor cells and densities of tumor infiltrating lymphocytes (TILs) in the surgical specimens of ESCC tissues were characterized using immunohistochemical assays. Uni- and multivariate analyses were performed to evaluate the prognostic value of B7-H4 expression levels and densities of TILs in tumor sections. Positive B7-H4 immunostaining was observed in 107 of 112 (95.5%) of ESCC tissue sections. We further divided all patients into two major subgroups, a lower B7-H4 expression group with 46 patients and a higher B7-H4 expression group with 66 patients. We found that expression levels of B7-H4 on tumor cells were significantly correlated with patient's gender (P = 0.0288), distant metastasis (P = 0.0500), and TNM stage (P = 0.0258). Moreover, tumor cell B7-H4 expression was inversely correlated with densities of CD3(+) T cells in tumor nest (P = 0.0424) and CD8(+) T cells in tumor stroma (P = 0.0229). The overall survival rate of the patients with higher B7-H4 expression was significantly worse than that of the patients with lower B7-H4 expression (P = 0.0105, Hazard Ratio: 1.854, 95%CI:1.152-2.902). Markers of cell-mediated immune responses such as CD3, CD8, and T-bet were associated with better patient survival. The present study demonstrated that B7-H4 expression in human ESCC is associated with cancer progression, reduced tumor immunosurveillance and worse patient outcomes. B7-H4 can serve as a novel prognostic predictor for human ESCC and a potential target for the immune therapy against this malignancy.
authors.affiliation: Institute of Medical Biotechnology, Medical College of Suzhou University, 708 Renmin Road, Suzhou, Jiangsu, China.
authors.forename: Lu-jun
authors.initials: LJ
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Hong-ya
authors.initials: HY
authors.lastname: Wu
authors.forename: Shu-ming
authors.initials: SM
authors.lastname: Zhou
authors.forename: Yan
authors.initials: Y
authors.lastname: Tan
authors.forename: Ming
authors.initials: M
authors.lastname: Tan
authors.forename: Bao-en
authors.initials: BE
authors.lastname: Shan
authors.forename: Bin-feng
authors.initials: BF
authors.lastname: Lu
authors.forename: Xue-guang
authors.initials: XG
authors.lastname: Zhang
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality*; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D059016:Tumor Microenvironment; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1
chemical_list: D018122:B7-1 Antigen; D060907:V-Set Domain-Containing T-Cell Activation Inhibitor 1; C475826:VTCN1 protein, human