FOXM1 expression correlates with tumor invasion and a poor prognosis of colorectal cancer.
FOXM1, a member of the Forkhead Box (Fox) family of transcription factors, plays a critical role in tumor development and metastasis. The aim of this study was to elucidate its role in colorectal cancer (CRC), particularly prognosis and metastasis. Semi-quantitative RT-PCR and Western blot assays were used to measure the expression levels of FOXM1 mRNA and protein in 15 CRC and adjacent normal mucosa tissues. Immunohistochemical assay was performed to detect FOXM1 protein expression in 112 CRC tissues and further determine its clinicopathological and prognostic significance. RNA interference (RNAi) was used to knockdown endogenous FOXM1 expression in CRC cell lines and to analyze the effects of FOXM1 knockdown on migration and invasion of CRC cells. The relative expression levels of FOXM1 mRNA and protein were significantly higher in CRC tissues than in adjacent normal mucosa tissues (P<0.01). In addition, the immunostaining of FOXM1 protein was stronger in CRC tissues than in adjacent normal mucosa tissues. By statistical analysis, we showed that high FOXM1 expression was closely correlated with the presence of lymph node metastasis, incidence of liver metastasis, and advanced TNM stage. Moreover, the cumulative 5-year survival rate of CRC patients with high FOXM1 expression was lower than that of those with low FOXM1 expression (P=0.0047). Multivariate analysis showed that the status of FOXM1 expression was an independent prognostic factor for CRC patients (P=0.025). Furthermore, RNAi-mediated FOXM1 knockdown could significantly inhibit growth, migration and invasion of CRC cells. Our results showed that FOXM1 over-expression is a molecular marker predicting increased invasive/metastatic potential of CRC and a poorer prognosis.
Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Jiangsu, China. xiaoyuanchu55@yahoo.com.cn
Xiao-Yuan
XY
Chu
Zi-Man
ZM
Zhu
Long-Bang
LB
Chen
Jing-Hua
JH
Wang
Quan-Sheng
QS
Su
Ji-Rong
JR
Yang
Yong
Y
Lin
Li-Jun
LJ
Xue
Xiao-Bei
XB
Liu
Xiao-Bei
XB
Mo
D000368:Aged; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D034741:RNA, Small Interfering