S100A6 as a potential serum prognostic biomarker and therapeutic target in gastric cancer.
BACKGROUND
Increased expression of S100A6 in many cancer tissues and its association with tumor behavior and patient prognosis were demonstrated, and there are no studies analyzing the serum levels of S100A6 in patients with gastric cancer (GC).


OBJECTIVE
Serum S100A6 levels were investigated as a marker of tumor aggressiveness in patients with GC, and the S100A6 gene was examined as a potential therapeutic target in GC.


METHODS
Serum S100A6 levels were detected in 103 GC patients and 72 healthy subjects by ELISA. Clinicopathological features of GC patients were analyzed in correlation to serum S100A6 levels. Two small interfering RNAs against S100A6 (siRNA1-S100A6 and siRNA2-S100A6) were generated and transfected into SGC7901 cells using pSUPER gfp-neo vector, and the effects of S100A6 knockdown on cell proliferation, invasion and apoptosis were evaluated in vitro. The effects of S100A6 silencing on tumor growth and metastasis were evaluated in vivo in a pseudo-metastatic GC nude mouse model.


RESULTS
Serum S100A6 levels were significantly higher in GC patients than in healthy controls (P < 0.001). Serum S100A6 levels were significantly correlated with lymph node metastasis, TNM stage, perineural invasion and vascular invasion. Serum S100A6 level was an independent predictor of overall survival. SiRNA-mediated silencing of S100A6 significantly induced apoptosis and decreased proliferation, clone formation and the invasiveness of GC SGC7901 cells in vitro and significantly reduced tumor volume and number in vivo (P < 0.01).


CONCLUSIONS
Serum S100A6 level may serve as a potential prognostic biomarker in GC. Inhibition of S100A6 decreased the metastatic potential of GC cells.
Department of General Surgery, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266509, Shandong, China, zhangjianli6551@126.com.
Jianli
J
Zhang
Kejun
K
Zhang
Xiuli
X
Jiang
Jian
J
Zhang
D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000037:antagonists & inhibitors / Q000097:blood* / Q000235:genetics; D001808:Blood Vessels / Q000473:pathology; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000097:blood* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D020868:Gene Silencing; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010525:Peripheral Nerves / Q000473:pathology; D011379:Prognosis; D034741:RNA, Small Interfering; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000037:antagonists & inhibitors / Q000097:blood* / Q000235:genetics; D013274:Stomach Neoplasms / Q000097:blood* / Q000473:pathology*; D015996:Survival Rate
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C055351:S100A6 protein, human