TWIST1 overexpression is associated with nodal invasion and male sex in primary colorectal cancer.
BACKGROUND
TWIST1 is a basic helix-loop-helix (bHLH) transcription factor that has been involved in tumor progression and metastasis in several cancer types, although no evidence has been provided yet on its implication in colorectal carcinogenesis.


METHODS
We examined the expression pattern of TWIST1 messenger RNA (mRNA) in 54 colorectal cancer biopsies compared with each respective adjacent normal mucosa by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) methodology.


RESULTS
TWIST1 mRNA was found significantly overexpressed in colorectal cancer samples compared to nontumorous colon mucosa (P < 0.0001). Receiver operating characteristic (ROC) curve analysis demonstrated that TWIST1 mRNA levels are significantly increased in patients with nodal invasion and, interestingly, a significant correlation with patient sex was also found.


CONCLUSIONS
Evidence for upregulation of TWIST1 mRNA in colorectal cancer is provided, suggesting its implication in the onset of malignant progression of this disease. In addition, significant higher levels of TWIST1 mRNA were found in men than in women, suggesting a possible transcriptional regulation of TWIST1 by sexual hormones. The use of TWIST1 as a new prognostic marker of advanced malignancy, and as a potential therapeutic target in colorectal cancer, is proposed.
Valdés-Mora
Fátima
F
Centro Nacional de Biotecnología, C/ Darwin, 3. Campus Cantoblanco, 28049, Madrid, Spain.
Gómez del Pulgar
Teresa
T
Bandrés
Eva
E
Cejas
Paloma
P
Ramírez de Molina
Ana
A
Pérez-Palacios
Rosa
R
Gallego-Ortega
David
D
García-Cabezas
Miguel Angel
MA
Casado
Enrique
E
Larrauri
Javier
J
Nistal
Manuel
M
González-Barón
Manuel
M
García-Foncillas
Jesús
J
Lacal
Juan Carlos
JC
D000368:Aged; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes; D008207:Lymphatic Metastasis; D008297:Male; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D051879:Twist-Related Protein 1 / Q000235:genetics*
D009687:Nuclear Proteins; D012333:RNA, Messenger; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1