Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Proteomic Analyses of Serial Prediagnostic PLCO Serum in Cases and Controls to Identify Early Detection Ovarian Cancer Biomarkers Rising in a Substantial Fraction of Cases and Stable in Most Controls

Award Number: U01CA260758
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2026

Group Awards By:

View Award Description

Proteomic Analyses of Serial Prediagnostic PLCO Serum in Cases and Controls to Identify Early Detection Ovarian Cancer Biomarkers Rising in a Substantial Fraction of Cases and Stable in Most Controls - Project Summary This project aims to discover and validate plasma biomarkers for the early detection of ovarian cancer. A hallmark of cancer is uncontrolled cell division, leading to a doubling time of the tumor. This exponential growth stands in stark contrast to the stable or slowly changing profile of plasma proteins in almost all other diseases or in healthy subjects. This project will leverage this unique hallmark to discover and validate plasma protein biomarkers for the early detection of ovarian cancer. We will discover early detection (ED) plasma protein biomarkers by identifying the proteins that significantly rise over time in an exponential fashion in a substantial fraction of cases and yet remain relatively stable over time in most controls. This requires plasma assays over a large suite of proteins with CVs lower than the protein's biological variation over time which can be as low as a CV of 10%. Furthermore, a low volume requirement is essential for access to precious biospecimens formed from long-term large early detection trials. Olink AB has developed proximity extension assays (PEAs) for a suite of ~1,500 proteins with CVs ranging from 6-12% and with a minimal volume requirement of 3 µL. Applying the Olink proteomic assays to serial pre-diagnostic plasma from subjects in the PLCO who were diagnosed with ovarian cancer during the study (cases n=50) and to serial plasma samples from a 4:1 matched control (n=200) : case (n=50) cohort will provide longitudinal data on ~1,500 plasma proteins from cases and controls by which to identify ED candidate biomarkers. Prior to cancer developing in each case, a biomarker will be stable over time, while after cancer inception the biomarker will rise exponentially reflecting tumor doubling. This behavior is represented by a change-point model in cases while the same biomarker in women without ovarian cancer (controls) will have a flat profile. ED biomarkers will be the proteins which have a change-point in a substantial fraction of cases while remaining stable in most (98%) controls. We will identify the top 20 ED biomarkers where the criteria for inclusion is a combination of fraction of cases, complementarity to proteins already selected, and time of rise with earlier risers having priority. After identification of the 20 ED biomarkers, Olink will develop a custom panel of 20 ED markers with absolute quantification. The custom panel will assay the same PLCO plasma samples as used in discovery. These data will be analyzed with a multivariate longitudinal change-point model to form a multiple marker longitudinal algorithm for ED. This classifier will be locked down. The classifier will be validated by assaying the custom panel of 20 ED biomarkers on an independent PLCO serial plasma sample set, from cases (n=50) and 10:1 matched controls (n=500). From these data the classifier will be assessed for two dimensions of sensitivity for early detection: (i) the number of months prior to detection in PLCO, and (ii) proportion of cases detected, while (iii) maintaining a high specificity goal of 98% - or a false positive rate of 2%. This low false positive rate requires a large number of controls (n=500) for its accurate assessment.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $693,443 )
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	001	5	9/4/2025	NON-COMPETING CONTINUATION	$451,184
2025	2025	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	5	8/15/2025	NON-COMPETING CONTINUATION	$242,259
														Subtotal = $693,443

Issue Date FY: 2024 ( Subtotal = $390,494 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	4	8/30/2024	NON-COMPETING CONTINUATION	$390,494
														Subtotal = $390,494

Issue Date FY: 2023 ( Subtotal = $119,967 )
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	3	8/15/2023	NON-COMPETING CONTINUATION	$119,967
														Subtotal = $119,967

Issue Date FY: 2022 ( Subtotal = $524,401 )
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	2	9/9/2022	NON-COMPETING CONTINUATION	$524,401
														Subtotal = $524,401

Issue Date FY: 2021 ( Subtotal = $546,231 )
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	1	9/15/2021	NEW	$546,231
														Subtotal = $546,231

Grand Total All Awards = $2,274,536

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Proteomic Analyses of Serial Prediagnostic PLCO Serum in Cases and Controls to Identify Early Detection Ovarian Cancer Biomarkers Rising in a Substantial Fraction of Cases and Stable in Most Controls

Award Number: U01CA260758

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/15/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer