间质细胞
免疫组织化学
肝星状细胞
癌症
癌症研究
癌细胞
癌相关成纤维细胞
医学
病理
肿瘤科
生物
内科学
作者
Satoe Numakura,Hiroshi Uozaki
标识
DOI:10.21873/anticanres.16964
摘要
"Stromal high expression" of Nicotinamide N-methyltransferase (NNMT), previously reported as a poor prognostic factor of gastric cancer, was based on immunohistochemical H-score. However, this could simply indicate an increase in cancer-associated fibroblasts (CAFs) because NNMT is positive for fibroblasts. To verify this, the proportion and staining intensity of stromal NNMT-positive stellate/spindle cells were evaluated separately and examined for its association with related proteins (H3K4me3, H3K27me3, and LOXL2).Immunohistochemistry for NNMT, H3K4me3, H3K27me3, and LOXL2 was performed on 521 tissue microarrays of gastric cancer. Cancer stromal stellate/spindle cells were evaluated according to morphology, proportion, and stain intensity of NNMT, loss of H3K4me3 and H3K27me3, and stain intensity of LOXL2. Their associations with clinicopathological characteristics and overall survival were examined.Higher staining intensity of NNMT was not related to a poorer prognosis. However, higher proportion of NNMT-positive stellate/spindle cells indirectly contributed to a poor prognosis. It was associated with CAF-like morphology and a global decrease in H3K4me3/H3K27me3, which were both associated with high LOXL2 expression. These three factors were independent poor prognostic factors. In addition, in the LOXL2-high group, prognosis significantly deteriorated with the presence of a global decrease in H3K4me3/H3K27me3.The higher proportion of NNMT-positive cancer stromal cells in gastric cancer serves as an indicator for identifying unfavorable prognostic CAFs that show a global decrease in H3K4me3/H3K27me3. This facilitates research on the nature of these cells and their characteristics.
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