title: S100A8+stroma cells predict a good prognosis and inhibit aggressiveness in colorectal carcinoma.
abstract: Gene microarray and bioinformatic analysis showed thatS100A8was more abundant in the stroma surrounding tumor buddings (TBs) than in the stroma surrounding primary tumor cells in colorectal carcinomas. Here, S100A8+cells in 419 colorectal carcinoma samples were stained by immunohistochemistry and counted using Image-pro plus 6.0. TBs were also counted and biomarkers associated with the epithelial-mesenchymal transition and apoptosis were assessed by immunohistochemistry. We evaluated the association between S100A8+cells and clinico-pathological variables as well as survival. Migration and invasion as well as biomarkers of the epithelial-mesenchymal transition and apoptosis were tested in CRC cells, treated with graded concentrations of recombinant human S100A8 protein. We found that the density of S100A8+cells in the tumor invasive front (S100A8+TIF) clearly distinguished patients with 5-y survival from those who did not survive (p= 0.01). The S100A8+-associated tumor budding (SATB) index determined by the S100A8+TIFand TB was an independent predictor of overall survival (p= 0.001) other than the S100A8+TIFor TB alone. Migration and invasion properties of CRC cells were inhibited by recombinant human S100A8 treatment. The particular S100A8+cells in the stroma were associated with important biomarkers of the epithelial-mesenchymal transition (E-cadherin and SNAIL) and apoptosis (BCL2). In conclusion, S100A8+cells in the stroma predict a good prognosis in colorectal carcinoma. An index combining S100A8+cells and TB independently predicts survival. Recombinant human S100A8 inhibited CRC cell migration and invasion, which was involved in epithelial-mesenchymal transition (E-cadherin and SNAIL) and apoptosis (BCL2).
authors.affiliation: Department of Pathology and Pathophysiology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University , Hangzhou, China.
authors.forename: Si
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pathology and Pathophysiology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University , Hangzhou, China.
authors.forename: Fangying
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Pathology and Pathophysiology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University , Hangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathology and Pathophysiology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University , Hangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Pathophysiology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University , Hangzhou, China.
authors.forename: Anjing
authors.initials: A
authors.lastname: Zhong
authors.affiliation: Department of Pathology, The First Peoples Hospital of Xiaoshan , Hangzhou, Xiaoshan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Pathology and Pathophysiology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University , Hangzhou, China.
authors.forename: Maode
authors.initials: M
authors.lastname: Lai
keywords: EMT; S100A8; immune microenvironment; invasion; migration; prognosis; tumor budding