PURPOSE: The peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that regulates expression of mediators of lipid metabolism and the inflammatory response. Thyroid hormone receptor-associated proteins 220 (TRAP220) is an essential component of the TRAP/Mediator complex. The objective of this study was to clarify whether PPARgamma or TRAP220 are significant prognostic markers in resectable colorectal cancer (CRC). MATERIALS AND METHODS: A total of 399 patients who underwent curative resection for CRC were enrolled. We investigated the presence of PPARgamma and TARP220 in CRC tissues and adjacent normal tissues by immunohistochemistry. Correlation between the expression of these factors and clinicopathologic features and survival was investigated. RESULTS: Median age of the patients was 63 years (range, 22 to 87 years), and median follow-up duration 61.1 months (range, 2 to 114 months). PPARgamma and TRAP220 expression showed significant correlation with depth of invasion (p=0.013 and p=0.001, respectively). Expression of TRAP220 also showed association with lymph node metastasis and TNM stage (p=0.001). Compared with patients with TRAP220 negative tumors, patients with TRAP220 positive tumors had longer 5-year disease-free survival (DFS) tendency (p=0.051). Patients who were PPARgamma positive combined with TRAP220 positive had a better 5-year DFS (64.8% vs. 79.3%, p=0.013). In multivariate analysis expression of both PPARgamma and TRAP220 significantly affected DFS (hazard ratio, 0.620; 95% confidence interval, 0.379 to 0.997; p=0.048). CONCLUSION: TRAP220 may be a valuable marker for nodal metastasis and TNM stage. Tumor co-expression of PPARgamma and TRAP220 represents a biomarker for good prognosis in CRC patients.
Colorectal Neoplasms* ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lipid Metabolism ; Lymph Nodes ; Mediator Complex Subunit 1* ; Multivariate Analysis ; Neoplasm Metastasis ; Peroxisomes* ; PPAR gamma* ; Prognosis ; Thyroid Gland

MED1 is a key transcription co-activator subunit of the Mediator complex that is essential for RNA polymerase II-dependent transcription. MED1 functions as a co-activator for PPARs and other nuclear receptors and transcription factors, and plays an important role in lipid metabolism. To examine how MED1 might affect plasma lipids, plasma triglyceride, cholesterol levels, and lipoprotein profiles, were measured in MED1(deltaLiv) mice fasted for 24, 48 and 72 hours. Histological changes in liver sections from MED1(deltaLiv) mice after 72 hours of fasting were also examined using H&E staining. There was no fat accumulation in livers of MED1(deltaLiv) mice compared to MED1(fl/fl) and PPARalpha -/- control mice after 72 hours of fasting. Compared with MEDl(fl/fl) mice, plasma triglycerides in MED1(deltaLiv) mice were significantly increased after 24, 48 and 72 hours of fasting, and plasma cholesterol was significantly increased after 48 and 72 hours of fasting. Lipoprotein profiles were similar in fed MED1(fl/fl) and MED1(deltaLiv) mice. However, very low density lipoprotein (VLDL) was significantly increased in MED1(deltaLiv) mice after 24 hours of fasting. We conclude that, hyperlipidemia in MED1(deltaLiv) mice in response to fasting is due to the accumulation of VLDL, which suggests that MED1 plays a pivotal role in the regulation of plasma triglyceride and cholesterol levels.
Animals ; Cholesterol ; blood ; Fasting ; Hyperlipidemias ; blood ; Lipoproteins, VLDL ; blood ; Liver ; chemistry ; Mediator Complex Subunit 1 ; genetics ; physiology ; Mice ; Mice, Knockout ; Triglycerides ; blood

OBJECTIVETo study the relationship of GYPC and TRIP3 gene expression and the prognosis of acute lymphoblastic leukemia (ALL) in children in order to explore the molecular biological mechanisms of recurrence and remission of ALL.

METHODSThirty-eight newly diagnosed ALL children were enrolled. Of the 38 patients, 31 achieved complete remission (CR) and 12 relapsed. Semi-quantitative RT-PCR was employed to measure blood GYPC and TRIP3 gene expression. Twenty blood samples from normal children were used as controls.

RESULTSBlood GYPC expression in newly diagnosed ALL children was significantly higher than that in the control group (p<0.01) and the CR group (p<0.01). The expression of GYPC gene in the CR group was similar to that in the control group. Other than the control group (p<0.01) and the CR group (p<0.01), the GYPC expression of the relapse group was significantly higher than that in the newly diagnosed group (p<0.01). The CR group showed lower GYPC gene expression than the nonjremission group before treatment (p<0.05). Blood expression of TRIP3 gene in the newly diagnosed and the relapse groups was significantly lower than that in the control group (p<0.05). The CR group had increased TRIP3 gene expression compared with the control group (p<0.01) as well as the newly diagnosed and the relapse groups (p<0.01). Of the 38 newly diagnosed ALL children, the patients with positive TRIP3 expression showed higher remission rate than those with negative TRIP3 (p<0.05). The TRIP3 gene expression before treatment in patients who achieved CR was higher than that in non-remission patients (p<0.05).

CONCLUSIONSA high GYPC gene expression is associated with an unfavorable outcome, in contrast, a high TRIP3 gene expression is associated with a favorable outcome in childhood ALL.

Adolescent ; Child ; Child, Preschool ; Female ; Glycophorin ; genetics ; Humans ; Infant ; Male ; Mediator Complex Subunit 1 ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; mortality ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors ; genetics