In this proposal, we have found the germ cell-specific gene TDRD1 is a potential novel prostate cancer gene. In normal tissues, TDRD1 is exclusively expressed in the germ cells. Strikingly, TDRD1 is overexpressed in 68% of human prostate tumors, indicating TDRD1 as a novel prostate cancer biomarker. Furthermore, at mRNA levels, TDRD1 expression is linked to favorable clinical outcome for prostate cancer patients, indicating that TDRD1 has prognostic value. Taken together, our preliminary results suggest that TDRD1 may be a novel prostate tumor biomarker with diagnostic and prognostic value, and as an ERG target gene, TDRD1 may have biological functions impacting prostate cancer initiation and progression. Importantly, we have successfully developed a mouse monoclonal antibody that recognizes human TDRD1 protein with exceptional specificity and sensitivity, in a variety of assays, including Western Blot analysis and Immunohistochemistry (IHC) staining on Formalin-fixed paraffin-embedded (FFPE) human prostate tumor samples. Using this anti-TDRD1 antibody, we have demonstrated that full length TDRD1 protein (~130 kDa) is expressed in the majority of human prostate cancer samples, but not in adjacent normal prostate tissues. This antibody will be an extremely valuable tool to determine the expression of TDRD1 by IHC in human prostate samples, including prostate needle biopsies. In this application, we will investigate the role of TDRD1 in human prostate cancer development, diagnosis, and prognosis by the following three specific aims.
Aim 1 will evaluate TDRD1 as a diagnostic marker by IHC staining of prostate needle biopsies with limited cancer.
Aim 2 will determine whether TDRD1 protein has prognostic value by IHC in clinically localized cancer.
Aim 3 will investigate the in vivo function of TDRD1 in prostate cancer development by using (a) prostate cancer cell line xenograft mouse models and (b) transgenic mouse model with prostate-specific overexpression of TDRD1. Results from Aim 1 and 2 could be quickly translated into a new tool for prostate cancer diagnosis and/or prognosis prediction in the clinic. Results from Aim 3 will shed light on the function of TDRD1 in prostate cancer development.
In our preliminary study, we have found a new prostate cancer gene TDRD1. In this proposal, we will evaluate its potential as a novel prostate cancer diagnostic and prognostic biomarker, and also investigate its role in prostate cancer development. Our results could be quickly translated into a new tool for prostate cancer diagnosis and/or prognosis prediction in the clinic.
|Li, Yujing; Liu, Yunhua; Xu, Hanchen et al. (2018) Heterozygous deletion of chromosome 17p renders prostate cancer vulnerable to inhibition of RNA polymerase II. Nat Commun 9:4394|
|Hai, Lan; Szwarc, Maria M; He, Bin et al. (2018) Uterine function in the mouse requires speckle-type poz protein. Biol Reprod 98:856-869|