title: Identification of S100A8 and S100A9 as negative regulators for lymph node metastasis of gastric adenocarcinoma.
abstract: 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.
authors.affiliation: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, Busan, Korea.
authors.forename: Jin Hwa
authors.initials: JH
authors.lastname: Choi
authors.forename: Na Ri
authors.initials: NR
authors.lastname: Shin
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Moon
authors.forename: Chae Hwa
authors.initials: CH
authors.lastname: Kwon
authors.forename: Gwang Ha
authors.initials: GH
authors.lastname: Kim
authors.forename: Geun Am
authors.initials: GA
authors.lastname: Song
authors.forename: Tae Yong
authors.initials: TY
authors.lastname: Jeon
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Dong Hun
authors.initials: DH
authors.lastname: Kim
authors.forename: Do Youn
authors.initials: DY
authors.lastname: Park
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D040501:Calgranulin A / Q000235:genetics / Q000378:metabolism*; D040502:Calgranulin B / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D040501:Calgranulin A; D040502:Calgranulin B