Utilization the Oncomine Database to Study the Aberrant Expression of Thyroid Hormone Receptor Regulated Genes in Human Cancer and Their Clinical Significance

Recently, Hassan et al. reported that hypothyroidism patients associate with a significantly elevated risk of hepatocellular carcinoma (HCC) in women, which was independent risk factor of HCC. Additionally, hypothyroidism and low-normal free T4 are related with an increased risk of breast cancer in postmenopausal women. It also reported that hypothyroidism enhances tumor invasiveness and the development of metastasis. These data indicate that thyroid hormone receptors (TRs) may play a tumor-suppressor role in normal physiological conditions. TRs possibly lose their suppressor function in the hypothyroidism condition (without T3), thus inducing cancer. In contrast, in the WNT-activated condition, TR1 plays a tumor promoter role in the intestine. Therefore, questions arise pertaining to the role of TRs during tumorigenesis and the nature of the underlying mechanism. However, previous studies in my laboratory were focused on in vitro. Currently, we selected TR-target genes from clinical database (Oncomine) combined with our previous T3-regulated database. Hopefully, we can select a group of T3-regulated genes which aberrantly express in HCC to determine the significant role of TR during tumoregenesis. We propose four specific aims to test our hypothesis. Specific Aim 1: To determine the aberrantly express genes regulated by T3 in HCC tissue, Oncomine cancer microarray databases will be analyzed and the results will be combined with T3-regulated gene database analyzed by oligo-microarray previously. A group of candidate genes will be selected. Specific Aim 2: The clinic significance of candidate genes which regulated by T3 as well as aberrantly express in HCCs will be determine in clinical specimens. Specific Aim 3: Functional study of the role of T3-regulated candidate genes in HCC cells. Specific Aim 4: Characterization of the signaling pathway of T3-regulated candidate genes in HCC cells. Significance of the proposal: 1) it will offer a strategy to global identification T3/TR regulated genes in clinical databases and 2) it will provide fundamental knowledge to explore the clinical significance of T3/TR regulated genes in cancer. The newly identified genes in this study will be used for diagnosis and prognosis, or for the future development of novel therapeutic targets. Finally, the molecular or cellular mechanisms of the action of genes in cancer progression will be established.

Project ID:PC10501-1547
External Project ID:MOST103-2320-B182-018-MY3