High expression of COUP-TF II cooperated with negative Smad4 expression predicts poor prognosis in patients with colorectal cancer.
OBJECTIVE
In order to evaluate whether the role of chicken ovalbumin upstream promoter transcription factor II (COUP-TF II) could sever as a predictor to stratify risk of human colorectal cancer (CRC) patients, and to elucidate the preliminary molecular mechanisms of COUP-TF II involved in the development and advancement of CRC reflected by investigating the relationship of COUP-TF II with PTEN, Smad4.


METHODS
112 cases tissue microarray and immunohistochemical SP method were used to detect the expression of COUP-TF II, PTEN and Smad4 in CRC tissues and adjacent non-tumorous tissues. The clinical relevance and prognosis of COUP-TF II, PTEN, Smad4 in CRC patients were analyzed. Furthermore, Cox proportional hazards model was performed to indicate the independent prognostic factors for CRC patients using various clinicopathological parameters and COUP-TF II, PTEN and Smad4.


RESULTS
COUP-TF II proteins were positively expressed in 65.2% of CRC tissues and 15.5% paired non-CRC tissues, respectively. The expression of COUP-TF II was significantly correlated with TNM stage and lymph node metastasis and a negative correlation with Smad4 expression. Patients bearing higher levels of COUP-TF II expression showed lower DFS and OS. Most importantly, Cox proportional hazards regression analyses showed COUP-TF II positive/Smad4 negative status (DFS, P=0.001; OS, P=0.005) were independent prognostic factors for CRC patients.


CONCLUSIONS
Positive COUP-TF II expression levels has significant value in determining CRC stage and metastasis and cooperates with negative Smad4 expression contributing to assess prognosis in patients with colorectal cancer, suggesting Smad4 may be involved in the above regulation progress probably.
College of Basic and Forensic Medicine, Sichuan University Chengdu 610041, Sichuan, China ; Department of Pathology, Xuzhou Medical College Xuzhou 221004, Jiangsu, China.
Chaoqun
C
Wang
Department of Radiation Oncology, Xuzhou City Central Hospital Xuzhou 221004, Jiangsu, China.
Yun
Y
Zhou
College of Basic and Forensic Medicine, Sichuan University Chengdu 610041, Sichuan, China.
Ruoyun
R
Ruan
Department of Pathology, Xuzhou Medical College Xuzhou 221004, Jiangsu, China.
Maojin
M
Zheng
Department of Pathology, Xuzhou Medical College Xuzhou 221004, Jiangsu, China.
Wencan
W
Han
College of Basic and Forensic Medicine, Sichuan University Chengdu 610041, Sichuan, China.
Linchuan
L
Liao
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D051837:COUP Transcription Factor II / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000032:analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D051901:Smad4 Protein / Q000032:analysis*; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D051837:COUP Transcription Factor II; D051059:PTEN Phosphohydrolase; D051901:Smad4 Protein; C497796:SMAD4 protein, human; C494929:PTEN protein, human; C095569:NR2F2 protein, human
COUP-TF II; Colorectal neoplasm; PTEN; prognosis; smad4; tissue microarray