Nanotechnology-Based Detection of Novel microRNAs for Early Diagnosis of Prostate Cancer
Abstract
Principal Investigator (PI) Career Goals: Prostate cancer (PCa) is the most commonly diagnosed non-skin malignancy in males and is the second leading cause of cancer death in men in the United States. Prostate cancer accounts for about 233,000 of all newly diagnosed cancers and 29,480 of all male deaths in the United States (Source: http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2014/. In spite of widespread use of surgery, radiotherapy and chemotherapy, death rates have increased 27% (2014 report). Currently, PCa is monitored and managed by prostate-specific antigen (PSA) screening combined with digital rectal examination and histopathological evaluation of prostate needle biopsies. Although the PSA screening had a paradigm-shifting impact on the detection and management of PCa, in >60% of all PSA screen-detected cancers are slow-growing and would never impact upon longevity, but results in nearly 1.2 million prostatic biopsies annually. This lack of sensitivity and specificity of PSA testing has contributed to controversy over the value of early detection and has led to a significant "overtreatment." Therefore, an early diagnosis of PCa will be the need of hour. Hence, there is an urgent need for the identification/development of non-invasive blood/serum-based biomarker for an early detection of PCa as well as to differentiate between androgen-dependent to androgen-independent. According to the reports, microRNAs could be an ideal candidate to study PCa pathogenesis to identify early diagnosis markers to differentiate between aggressive PCa to non-aggressive. There are several miRNA detection techniques (qtPCR, Nothern blot, etc.), but there are certain Limitations, i.e., poor sensitivity, specificity, robust protocol, and cost-effectiveness. Therefore, we are introducing novel and advanced nanotechnology-based diagnosis methods for early detection of prostate cancer. This prostate cancer research training program will help the PI to combine his previous nanotechnology expertise and presently learned molecular biology and biochemical skills to conduct in vitro and in vivo model studies on prostate cancer. Altogether, the PI intends to take advantage of this opportunity to establish him as an independent investigator in prostate cancer research and to make contribution to the fight against prostate cancer in the future. Hypothesis: Invention of the advanced nanotechnology based early diagnostic tools for PCa via detection of blood serum (i.e., microRNA level) as a biomarker (indicator of the biological state of the disease. Aim I: Development of fluorescently labeled DNA-metal nanoparticle probes (i.e., nanoprobes) and their implementation in a simple strategy for direct microRNA quantification in Prostate cancer serum. Aim II: To investigate stage specific global microRNA expression profiles in the PCa tissue followed by their detection in mouse serum by using DNA-metal nanoparticle probes/nanoprobes. Aim III: Further investigation of the diagnostic potential of differentially expressed miRNAs in sera/serum of human PCa patients. Applicability of the Research: The PI training and research work plan hypothesized early-stage diagnosis of prostate cancer via innovated nanoprobes for detection of the microRNA level in the serum of the patient. Early-stage detection/diagnosis of PCa provides a much higher chance of treatment/novel therapeutic approaches for recovery of the cancer patient by preventing its natural progression. These findings will help us to design novel therapies treat the androgen-independent cancers. Application, Benefits and Risk: Overall, the proposed studies will be helpful for diagnosis of the PCa and also in identifying high-risk hormone-independent and aggressive forms of the disease.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510157
Entities
People
- Prakash Kshirsagar
Organizations
- United States Army
- University of Nebraska Medical Center