This project –A Comprehensive Program for the Validation of Prostate Cancer Early Detection with Novel Protein Identification Techniques -- is divided into three phases. The goal of Phase I was to assess the reproducibility and portability of Surface-Enhanced Laser Desorption and Ionization time-of-flight mass spectrometry (SELDI-TOF-MS) using protein profiles generated from serum. Phase I was recently successfully completed at six institutions using a single source of pooled sera.
The overall goal of Phase II is to develop and evaluate an algorithm for classifying cases and controls using protein profiles produced from SELDI-TOF-MS using serum collected from prostate cancer cases and non-cancer controls.
Objective 1 - Identification of biorepositories
Objective 2 - Generate protein profiles
Objective 3 - Construction of classifiers and development of algorithm.
Objective 4 – Validate the classifier constructed in Objective 3. If Objective 3, Aim 1, is successfully met
The DMCC will apply the boosting decision tree,11 the boosting logistic regression13, and other classification methods to identify a classification algorithm that has minimum Cross-Validation error. The performance of this classifier will be assessed with the following the intended clinical uses in mind: 1)For men with PSA > 4, the population by current practice undergone biopsies with 25% Positive Predicted Value (PPV) for positive biopsies, we could judge that the new test has clinical potential if on this population sensitivity is significantly better than 85% and specificity is significantly better than 50% (null hypothesis corresponding to PPV=36%). This question is answered by comparing the biopsy-negative non-cancer controls with each of two cancer groups (Gleason Score < 7, and 7 or greater), and combined. In order for the Phase II validation study has adequate power (85%), the target observed specificity for this classifier in training sample should be at least 65% at sensitivity fixed at 95% on ROC curve for all prostate cancers (Aim 1: two case groups combined and compared to controls). Aim 2 (Gleason 7 or greater prostate cancers compared to control and low grade prostate cancer groups combined) is considered as secondary because using Gleason Score 7 or greater as the cutoff point for high grade is more for feasibility rather reason (there are not enough prostate cancers with Gleason Score 8 or 9). 2) If the criterion for Aim 1 is satisfied, validation part of Phase II will proceed. If the observed sensitivity and specificity are significantly better than the values specified by null hypotheses but less than the target values, the study group will evaluate whether the observed performance still has potential clinical benefit, and if it does, whether to increase sample size for the validation part of Phase II.
There are currently no biomarkers annotated for this protocol.
The National Cancer Institute's Division of Cancer Prevention has released a new funding opportunity to solicit organ-specific applications for Biomarker Developmental Laboratories (BDLs), one of the four scientific units of the recently funded Early Detection Research Network (EDRN). The EDRN is a national infrastructure funded to discover, develop, and validate biomarkers for risk assessment, detection, and molecular diagnosis and prognosis of early cancer. BDLs are responsible for the discovery, development, characterization, and testing of new, or the refinement of existing, biomarkers and biomarker assays for risk assessment, detection, and molecular diagnosis and prognosis of cancers.
The existing BDLs are primarily focused on ovary and gastrointestinal cancers. The proposed BDLs (to be supported under this funding opportunity) should be focused on one or more of the following cancers: breast, prostate and other genitourinary organs, or lung. In addition, cancers with rapidly rising incidence rates, e.g., endometrial, hepatocellular, kidney, thyroid, oropharyngeal cancers, and/or cancers with unique etiology, e.g., mesothelioma, will be considered.
The newly funded units of the Early Detection Research Network will be announced later in April. Successful applicants have already been notified. Those researchers who were not successful during the last round of applications are encouraged to apply to this opportunity.