Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, Busan, Korea.
Histol Histopathol. 2012 Nov;27(11):1439-48. doi: 10.14670/HH-27.1439.
With increasing therapeutic use of minimally invasive therapy for treatment of early gastric cancer, prediction of lymph node metastasis is important. In search of tissue biomarkers for prediction of lymph node metastasis of gastric adenocarcinoma, we analyzed gastric adenocarcinoma tissue using proteomic methods. We have done 2D-PAGE and MALDI-TOF MS analysis in matched normal and gastric cancer tissues. We also evaluated the clinicopathological significance of expression of S100A8 and S100A9 in gastric adenocarcinoma using a tissue microarray of 218 gastric adenocarcinoma specimens. Cell invasion and migration assay were performed to confirm functional role of S100A8 and S100A9 using small hairpin RNA lentivirus. We identified 8 up-regulated and 5 down-regulated proteins in gastric cancer tissues compared to matched normal mucosa. Of these, expression of S100A8 and S100A9 occurred mainly in stromal cells and inflammatory cells between tumor cells. Correlation was observed between small lesion size, decreased depth of invasion, a tendency to absence of lymphovascular tumor emboli, a decrease in perineural invasion and lymph node metastasis, and expression of stromal S100A8. In addition, increased expression of stromal S100A9 in gastric adenocarcinoma was associated with small lesion size and a decrease in lymph node metastasis. Functional analysis confirmed that down-regulation of S100A8 and S100A9 by small hairpin RNA lentivirus induced an increase of migration and invasion in gastric cancer cell lines. Taken together, these findings suggest that S100A8 and S100A9 are negative regulators of lymph node metastasis of gastric adenocarcinoma and can be used as biomarkers for prediction of lymph node metastasis in gastric adenocarcinoma.
随着微创治疗早期胃癌的治疗应用不断增加，预测淋巴结转移变得非常重要。为了寻找预测胃腺癌淋巴结转移的组织生物标志物，我们使用蛋白质组学方法分析了胃腺癌组织。我们在匹配的正常和胃癌组织中进行了 2D-PAGE 和 MALDI-TOF MS 分析。我们还使用了 218 例胃腺癌标本的组织微阵列评估了 S100A8 和 S100A9 在胃腺癌中的表达的临床病理意义。通过小发夹 RNA 慢病毒进行细胞侵袭和迁移实验，证实了 S100A8 和 S100A9 的功能作用。与匹配的正常粘膜相比，我们在胃癌组织中鉴定出 8 种上调和 5 种下调的蛋白质。其中，S100A8 和 S100A9 的表达主要发生在肿瘤细胞之间的基质细胞和炎症细胞中。在小病变大小、浸润深度降低、无血管淋巴管肿瘤栓子、周围神经浸润减少和淋巴结转移减少之间观察到相关性，并且与基质 S100A8 的表达相关。此外，胃腺癌中基质 S100A9 的表达增加与小病变大小和淋巴结转移减少相关。功能分析证实，小发夹 RNA 慢病毒下调 S100A8 和 S100A9 可诱导胃癌细胞系的迁移和侵袭增加。总之，这些发现表明 S100A8 和 S100A9 是胃腺癌淋巴结转移的负调节剂，可作为胃腺癌淋巴结转移预测的生物标志物。
