S100A6 overexpression is associated with poor prognosis and is epigenetically up-regulated in gastric cancer.
S100A6 has been implicated in a variety of biological functions as well as tumorigenesis. In this study, we investigated the expression status of S100A6 in relation to the clinicopathological features and prognosis of patients with gastric cancer and further explored a possible association of its expression with epigenetic regulation. S100A6 expression was remarkably increased in 67.5% of gastric cancer tissues as compared with matched noncancerous tissues. Statistical analysis demonstrated a clear correlation between high S100A6 expression and various clinicopathological features, such as depth of wall invasion, positive lymph node involvement, liver metastasis, vascular invasion, and tumor-node metastasis stage (P < 0.05 in all cases), as well as revealed that S100A6 is an independent prognostic predictor (P = 0.026) significantly related to poor prognosis (P = 0.0004). Further exploration found an inverse relationship between S100A6 expression and the methylation status of the seventh and eighth CpG sites in the promoter/first exon and the second to fifth sites in the second exon/second intron. In addition, the level of histone H3 acetylation was found to be significantly higher in S100A6-expressing cancer cells. After 5-azacytidine or trichostatin A treatment, S100A6 expression was clearly increased in S100A6 low-expressing cells. In conclusion, our results suggested that S100A6 plays an important role in the progression of gastric cancer, affecting patient prognosis, and is up-regulated by epigenetic regulation.
Wang
Xiao-Hong
XH
Department of Surgery, Beijing Cancer Hospital & Institute, Peking University School of Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China.
Zhang
Lian-Hai
LH
Zhong
Xi-Yao
XY
Xing
Xiao-Fang
XF
Liu
Yi-Qiang
YQ
Niu
Zhao-Jian
ZJ
Peng
Yong
Y
Du
Hong
H
Zhang
Gui-Guo
GG
Hu
Ying
Y
Liu
Ni
N
Zhu
Yu-Bing
YB
Ge
Shao-Hua
SH
Zhao
Wei
W
Lu
Ai-Ping
AP
Li
Ji-You
JY
Ji
Jia-Fu
JF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000494:pharmacology; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008113:Liver Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D015854:Up-Regulation
D000964:Antimetabolites, Antineoplastic; D018797:Cell Cycle Proteins; D006877:Hydroxamic Acids; D011500:Protein Synthesis Inhibitors; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C055351:S100A6 protein, human; C012589:trichostatin A; D001374:Azacitidine