Expression of chicken ovalbumin upstream promoter-transcription factor II and liver X receptor as prognostic indicators for human colorectal cancer

Abstract

Cholesterol increases the risk of colorectal cancer. Liver X receptor (LXR), retinoid X receptor (RXR)α and sterol regulatory element binding protein (SREBP)-1c are transcriptional regulators of lipid metabolism. Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) serves an essential role in angiogenesis and development, but its role in cancer is controversial. The expression of COUP-TFII, LXR, RXRα and SREBP-1c in colorectal cancer, as well as their association with clinicopathologic features, was assessed, and their utility as prognostic indicators in colorectal cancer evaluated. Colorectal cancer samples (n=707 patients) were analyzed for COUP-TII, LXR, RXRα and SREBP-1c expression by immunohistochemistry. Overall survival curves of patients with tumors expressing different levels of these proteins were produced and risk factors were assessed. Of the 707 patients, 32.7, 50.9, 56.4, and 41.7% were positive for COUP-TFII, LXR, RXRα, and SREBP-1c, respectively. The lack of COUP-TFII or LXR expression was associated with lower overall survival rates (P=0.0154 for COUP-TFII, and 0.0113 for LXR). Following adjustment for other clinical risk factors (age, sex, tumor size, grade, vascular invasion, and Tumor-Node-Metastasis stage), the lack of COUP-TFII or LXR expression was a negative independent prognostic factor for survival. The expression of COUP-TFII and LXR alone or in combination may be biomarkers to indicate a positive prognosis in patients with colorectal cancer.

Keywords: chicken ovalbumin upstream promoter-transcription factor II; colorectal cancer; liver X receptor; prognosis; retinoid X receptor α.

Figure 1.

Representative images of immunohistochemical staining for COUP-TFII, LXR, RXRα, and SREBP-1c in colorectal cancer tissue. (A) Left, COUP-TFII-positive colorectal cancer tissue. Right, COUP-TFII-negative colorectal cancer tissue. (B) Left, LXR-positive colorectal cancer tissue. Right, LXR-negative colorectal cancer tissue. (C) Left, strong RXRα immunoreactivity detected in well-differentiated colorectal cancer tissues. Right, weak RXRα immunoreactivity detected in poorly differentiated colorectal cancer tissues. (D) Left, SREBP-1c-positive colorectal cancer tissue. Right, SREBP-1c-negative colorectal cancer tissue. Magnification, ×200. COUP-TFII, chicken ovalbumin upstream promoter-transcription factor II; LXR, liver X receptor; RXRα, retinoid X receptor α; SREBP-1c, sterol regulatory element binding protein-1c.

Figure 2.

Kaplan-Meier OS curves for 707 patients with colorectal cancer, according to expression levels of COUP-TFII, LXR, RXRα, and SREBP-1c. (A) Patients stratified according to COUP-TFII expression. (B) Patients stratified according to LXR expression. (C) Patients stratified according to RXRα expression. (D) Patients stratified according to SREBP-1c expression. OS rates are indicated in each panel. OS, overall survival; COUP-TFII, chicken ovalbumin upstream promoter-transcription factor II; LXR, liver X receptor; RXRα, retinoid X receptor α; SREBP-1c, sterol regulatory element binding protein-1c.

Figure 3.

Association between combinations of COUP-TFII and LXR expression and survival of patients with colorectal cancer. Kaplan-Meier OS curves for 707 colorectal cancer patients, according to the expression levels of COUP-TFII and LXR in combination. OS rates are indicated in each panel. OS, overall survival; COUP-TFII, chicken ovalbumin upstream promoter-transcription factor II; LXR, liver X receptor.