# Cellular Sources of Pathological Stromal Variants

> **NIH NIH R21** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 · $203,944

## Abstract

Hepatocellular carcinoma (HCC) accounts for >80% of primary liver cancers and is the fourth most common
cause of cancer-related death. Based on populations projections in 2005, HCC should have decreased by 8%
by the year 2015. However, HCC has tripled since 1980 and continues to grow while mortality has doubled.
Stroma changes are a primary feature in the pathological progression of HCC, molecular subtyping of HCC, and
are predictive of outcomes, yet the translational and post-translational modifications (PTMs) of stromal proteins
related to pathological cell status remains mostly unknown. Our preliminary data shows high complexity in
localization of stromal proteins and, particularly, changes in PTM site regulation of collagen hydroxylated prolines
(HYPs) localized to pathology. Stromal HYP variants can distinguish molecular subtypes of HCC that differe by
outcome, suggesting that HYP variants may have a direct association with survival and progression. From this
we hypothesize that A) Regionalized cell populations within the liver tissue have distinctive stromal signatures
that contribute to HCC subtypes; B) The PTM HYP sites are a primary regulator differentiating HCC pathology
subtypes in primary collagens collagen types α-1(I) chain (COL1A1), α-1(II) chain (COL1A2), and α-1(III) chain
(COL3A1); C) Stromal variants, including post-translational HYP modifications, represent a novel, clinically
significant contributor to HCC. The Aims work to define stromal variants co-localized to pathological cell status
by HCC molecular subtypes and determine the clinical significance of HCC stromal variants by investigating
variant regulation relative to progression by grade and stage as well as outcome. Characterization of stromal
variants due to pathological cell origin within the tumor microenvironment may help elucidate and/or monitor the
functional state of cancer associated fibroblasts contributing to subtype evolvement. We expect that this work
will lead to new mechanistic directions in targeting stroma for therapies and the results may be further developed
as ancillary clinical tools that help in patient management. A long-term goal is to improve targeting capabilities
of stromal therapies and eliminate HCC mortality.

## Key facts

- **NIH application ID:** 10439877
- **Project number:** 5R21CA263464-02
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Peggi M Angel
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $203,944
- **Award type:** 5
- **Project period:** 2021-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10439877

## Citation

> US National Institutes of Health, RePORTER application 10439877, Cellular Sources of Pathological Stromal Variants (5R21CA263464-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10439877. Licensed CC0.

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