Immunohistochemistry (IHC) is widely used to classify cancer and guide clinical management of patients. A major power of IHC is the detection of markers in the spatially resolved context of tumor tissue, including cancerous and stromal elements, individual cell types, and subcellular compartments. Quantitative Immunofluorescence (QIF) is used increasingly for IHC quantification of proteins that may serve as prognostic biomarkers or targets for specific cancer therapies. A common application of QIF is simultaneous slide-based analysis of certain protein expression using tissue microarrays (TMAs), which incorporate tumor tissues from large cohorts of patients. This technology combined with machine readers allows for high-throughput molecular profiling of tumor tissues and rapid development and validation of new prognostic and predictive cancer biomarkers. The overall goal of our proposal is to develop an analytical framework of for discovery of new IHC biomarkers to improve prognostication and drug response prediction. The new statistical methods will be tailored to use the rich and untapped information on cell-level protein expression levels. Novel QIF IHC biomarkers will be optimized as flexible indices based either on distribution functions of cell-level protein expressions or on the spatial localization of the IHC signals viewed as marks of the spatial point pattern of cancer cells. The proposed studies will yield broadly applicable methods for development of new biomarkers in cancer. The improved biomarkers would support rational recruitment of patients at elevated risk of recurrence into biomarker-driven clinical trials, with a potential to have major near-term impact on clinical research and reduce mortality from cancer.

Public Health Relevance

Cancer is a diverse set of diseases. Pathologists use antibody-based staining techniques to assess levels of tumor markers to classify cancers, so that surgeons and medical oncologists can provide optimal treatment. This project will develop superior methods for tumor biomarker quantification that would support rational recruitment of patients at elevated risk of recurrence into biomarker-driven clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA222847-03
Application #
10083722
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Ossandon, Miguel
Project Start
2019-02-01
Project End
2024-01-31
Budget Start
2021-02-01
Budget End
2022-01-31
Support Year
3
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107