Bone Marrow Extracellular Matrix Gene Expression Analysis for Cancer Prognosis and Bone Metastasis Prediction: An 82-Gene Panel Study Using PLCO Trial Data

Principal Investigator

Name
Shelly Peyton

Degrees
Ph.D.

Institution
Trustees of Tufts College

Position Title
Department Chair of Biomedical Engineering Program

Email
shelly.peyton@tufts.edu

About this CDAS Project

Study
PLCO (Learn more about this study)

Project ID
PLCO-2011

Initial CDAS Request Approval
Feb 4, 2026

Title
Bone Marrow Extracellular Matrix Gene Expression Analysis for Cancer Prognosis and Bone Metastasis Prediction: An 82-Gene Panel Study Using PLCO Trial Data

Summary
This research project aims to analyze mRNA expression data for a targeted panel of 82 genes related to bone marrow extracellular matrix (ECM) using data from the PLCO Cancer Screening Trial. The study will investigate the relationship between bone marrow ECM gene expression profiles and key clinical outcomes including overall survival, time to metastasis, and metastatic patterns across different demographic groups, with particular focus on bone metastasis given its prevalence in cancers such as breast cancer.
The project will utilize mRNA sequencing data to characterize expression levels of the 82 bone marrow ECM-related genes and correlate these molecular profiles with clinical endpoints including days until death, days until detected metastasis, and metastatic location. This approach is particularly relevant given that breast cancer has a well-established propensity for bone metastasis, and the bone marrow ECM plays a crucial role in creating a pre-metastatic niche that facilitates cancer cell colonization and growth in bone tissue. Additionally, we will examine how these relationships vary across different racial and ethnic populations to identify potential disparities in cancer outcomes and molecular signatures.
This analysis will contribute to our understanding of how bone marrow ECM components influence cancer progression and metastatic tropism, particularly to bone sites. The large, well-characterized PLCO cohort provides an ideal dataset for this investigation due to its comprehensive follow-up data, diverse participant population, and potential inclusion of cancers with varying bone metastatic potential.

Aims

Aim 1: Characterize Bone Marrow ECM Gene Expression Profiles Across Cancer Types
- Analyze mRNA expression levels for all 82 bone marrow ECM-related genes across prostate, lung, colorectal, and ovarian cancer cases in the PLCO cohort
- Identify bone marrow ECM gene expression patterns that distinguish between different cancer types
- Determine the distribution and variability of ECM-related gene expression levels within and across cancer types
- Compare expression patterns between cancers with high versus low bone metastatic potential

Aim 2: Investigate Associations Between Bone Marrow ECM Gene Expression and Survival Outcomes
- Examine the relationship between individual bone marrow ECM gene expression levels and overall survival (days until death)
- Develop multi-gene ECM expression signatures predictive of survival outcomes
- Assess whether bone marrow ECM gene expression profiles can stratify patients into distinct prognostic groups
- Evaluate the prognostic value of the 82-gene ECM panel compared to traditional clinical factors

Aim 3: Analyze Bone Marrow ECM Gene Expression in Relation to Metastatic Disease and Bone Tropism
- Investigate associations between bone marrow ECM gene expression profiles and time to metastasis detection (days until detected metastasis)
- Examine whether specific ECM gene expression signatures are associated with bone versus non-bone metastatic sites
- Identify bone marrow ECM genes whose expression levels may predict bone metastatic potential, drawing on established knowledge that breast cancer frequently metastasizes to bone
- Assess the temporal relationship between ECM gene expression changes and metastatic progression, particularly to bone sites
- Compare ECM gene expression patterns between patients who develop bone metastases versus those with metastases to other sites

Aim 4: Evaluate Racial and Ethnic Disparities in Bone Marrow ECM Gene Expression and Outcomes
- Compare bone marrow ECM gene expression profiles across different racial and ethnic groups within the PLCO cohort
- Investigate whether race/ethnicity modifies the relationship between ECM gene expression and clinical outcomes, particularly bone metastasis
- Identify population-specific molecular ECM signatures that may contribute to cancer health disparities in bone metastatic disease
- Assess whether the prognostic value of the 82-gene ECM panel varies by demographic characteristics

Collaborators

Shelly Peyton Tufts University
Tianna Edwards Tufts University