Abstract
Gene microarray and bioinformatic analysis showed that S100A8 was 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(+)(TIF) and TB was an independent predictor of overall survival (p = 0.001) other than the S100A8(+)(TIF) or 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).