Prostate cancer is the most prevalent type of cancer and it is the second highest contributor to cancer death among men in the U.S. A major issue in prostate cancer detection and therapy is that we currently have no method to reliably distinguish aggressive prostate cancer from non-aggressive prostate cancer. This leads to significant unnecessary suffering among prostate cancer patients. We hypothesize that specific glycoproteins or their glycosylation specifically altered in aggressive prostate cancer cells can be used as biomarkers to distinguish patients with aggressive from those with non-aggressive prostate cancer. We propose in four specific aims to develop novel glycoprotein biomarkers that can detect aggressive cancer in pre-surgical urine or biopsy tissues.
In Aim 1, we will analyze urinary glycoproteins from patients with aggressive cancer and non-aggressive cancer using high throughput glycoproteomics and mass spectrometry to identify glycoproteins associated with aggressive prostate cancer.
In Aim 2, we will validate the identified candidate urinary glycoproteins by targeted analysis of candidate glycoproteins from additional urine samples in independent testing sets of prostate cancer urine specimens from the EDRN network.
In Aim 3, we will develop highly sensitive, specific, and high throughput ELISA or mass spectrometry based selective reaction monitoring assays as noninvasive urine tests using the glycoprotein biomarkers identified and validated from Aim 1 and Aim 2 and validate the performance of the tests for aggressive prostate cancer biomarkers. We will further determine the clinical utility of the validated tests to detect patients with aggressive prostate cancer in active surveillance program.
In Aim 4, we will develop and optimize the immunohistochemistry assays for the glycoproteins associated aggressive prostate cancer tissues and validate these tissue glycoproteins using tissue microarrays. We will then further determine the clinical utility of the immunohistochemistry assays as biopsy based tissue tests for the early detection of patients with aggressive prostate cancer in active surveillance program. If successful, the identified and validated biomarkers will be tested by EDRN biomarker reference laboratory (BRL) and clinical validation center (CVC) in retrospective and prospective studies. Biomarkers capable of distinguishing aggressive from nonaggressive prostate cancer will allow men with aggressive prostate cancer to receive appropriate treatment earlier in the course of their diseases and prevent men with non- aggressive prostate cancer from overtreatment.
This project aims to develop glycoprotein biomarkers and determine their clinical utilities in distinguish men with aggressive prostate cancer from men with very low risk prostate cancer by developing noninvasive urine test or biopsy-based tissue tests.
|Osmani, Lais; Askin, Frederic; Gabrielson, Edward et al. (2018) Current WHO guidelines and the critical role of immunohistochemical markers in the subclassification of non-small cell lung carcinoma (NSCLC): Moving from targeted therapy to immunotherapy. Semin Cancer Biol 52:103-109|
|Höti, Naseruddin; Yang, Shuang; Hu, Yingwei et al. (2018) Overexpression of ? (1,6) fucosyltransferase in the development of castration-resistant prostate cancer cells. Prostate Cancer Prostatic Dis 21:137-146|
|Yang, Shuang; Clark, David; Liu, Yang et al. (2017) High-throughput analysis of N-glycans using AutoTip via glycoprotein immobilization. Sci Rep 7:10216|
|Inouye, Casey M; Anagnostou, Valsamo; Li, Qing Kay (2017) Primary parotid adenocarcinoma metastasis to the spleen with PIK3CA mutation: cytological findings and review of the literature. Int J Clin Exp Pathol 10:5999-6005|
|Yang, Shuang; Zhang, Lei; Thomas, Stefani et al. (2017) Modification of Sialic Acids on Solid Phase: Accurate Characterization of Protein Sialylation. Anal Chem 89:6330-6335|
|Shah, Punit; Yang, Weiming; Sun, Shisheng et al. (2017) Platelet glycoproteins associated with aspirin-treatment upon platelet activation. Proteomics 17:|
|Höti, Naseruddin; Shah, Punit; Hu, Yingwei et al. (2017) Proteomics analyses of prostate cancer cells reveal cellular pathways associated with androgen resistance. Proteomics 17:|
|Zhou, Jianliang; Yang, Weiming; Hu, Yingwei et al. (2017) Site-Specific Fucosylation Analysis Identifying Glycoproteins Associated with Aggressive Prostate Cancer Cell Lines Using Tandem Affinity Enrichments of Intact Glycopeptides Followed by Mass Spectrometry. Anal Chem 89:7623-7630|
|Yang, Shuang; Höti, Naseruddin; Yang, Weiming et al. (2017) Simultaneous analyses of N-linked and O-linked glycans of ovarian cancer cells using solid-phase chemoenzymatic method. Clin Proteomics 14:3|
|Liu, Yansheng; Gonzàlez-Porta, Mar; Santos, Sergio et al. (2017) Impact of Alternative Splicing on the Human Proteome. Cell Rep 20:1229-1241|
Showing the most recent 10 out of 78 publications