目的:“烟酰胺N-甲基转移酶(NNMT)的基质高表达”,先前报道为胃癌的不良预后因素,基于免疫组织化学H评分。然而,这可能仅仅表明癌症相关成纤维细胞(CAFs)的增加,因为NNMT对成纤维细胞呈阳性.为了验证这一点,我们分别评估了基质NNMT阳性星状/梭形细胞的比例和染色强度,并检查了其与相关蛋白(H3K4me3,H3K27me3和LOXL2)的相关性.
方法:NNMT的免疫组织化学,H3K4me3,H3K27me3和LOXL2在521个胃癌组织微阵列上进行。根据形态学评估癌基质星状/梭形细胞,比例,和NNMT的染色强度,H3K4me3和H3K27me3的损失,以及LOXL2的染色强度。检查了它们与临床病理特征和总生存率的关联。
结果:NNMT染色强度较高与预后较差无关。然而,NNMT阳性星状/梭形细胞比例较高间接导致预后不良.它与CAF样形态和H3K4me3/H3K27me3的整体减少有关,这两者都与高L0XL2表达有关。这三个因素均为预后不良的独立因素。此外,在LOXL2高组中,随着H3K4me3/H3K27me3的整体降低,预后显着恶化。
结论:胃癌中NNMT阳性癌基质细胞的比例较高,可作为确定H3K4me3/H3K27me3总体降低的不良预后CAFs的指标。这有助于研究这些细胞的性质及其特征。
OBJECTIVE: \"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).
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.