# Integrated Genomic-Transcriptomic Characterization to Identify Molecular Mechanisms of Disparities in PDAC Outcomes

> **NIH NIH R21** · UNIVERSITY OF IOWA · 2024 · $218,351

## Abstract

Despite advances in diagnostic and therapeutic modalities, the 5-year survival of patients with pancreatic
adenocarcinoma (PDAC) remains woefully low. Unfortunately, African Americans (AA) bear a significant brunt
of this disease and both the incidence and mortality of PDAC are higher amongst them. Understanding the
biological factors contributing to this pattern will help develop novel strategies to improve outcomes. Pancreatic
cancer is a mutation-driven cancer. Alterations in tumor driver genes like KRAS, TP53, SMAD4 and CDKN2A
alter multiple transcriptional pathways in the native pancreatic cells and their microenvironment, resulting in
tumor growth, progression and metastases. Presence or absence of many of these mutations can modulate
the aggressiveness of cancer and the clinical course of patients with PDAC. Studies in other cancers
including colon, breast and prostate cancer, have demonstrated that genomic and transcriptional
landscape can shape the incidence and the outcomes of these cancers. However, such data in the
context of PDAC is lacking. Thus, we have put forth the following hypothesis to explain the observed clinical
patterns in the context of PDAC:
Hypothesis: Differences in the genomic and transcriptomic signatures contribute to the observed patterns of
increased pancreatic cancer incidence and worse outcomes in AA patients. Our hypothesis will be tested
through the two specific aims: Aim 1 will be focused on interrogating the mutational landscape of PDAC using
deep whole exome sequencing (WES) on resected tumor specimens of histologically proven PDAC cases from
AA patients. In addition to testing specific hypotheses about KRAS, we will screen potential pathogenic
variants (PPVs) which could be contributing significantly clinical outcomes among PDAC patients. In Aim 2
Bulk RNA sequencing (RNA-seq) will be performed on the cohort of 100 PDAC specimens from AA patients
(from aim 1) to identify clinically relevant transcriptional pathways in PDAC tumors in two ways. First, the
PDAC cases will be compared according to our published PurIST algorithm to understand the incidence of
classical/basal tumor subtypes, which predict response to frontline therapy. Additionally, we will perform denovo
transcriptomic subtyping and pathway analysis to understand whether PDAC tumors harbor distinct
transcriptional signatures compared to those previously identified. Successful execution of the current studies
will provide, for the first time, detailed integrative analysis of genetic and transcriptional landscape of PDAC.
These data will help improve our understanding of the biological factors contributing to observed clinical
patterns and support the development of novel strategies to improve outcomes.

## Key facts

- **NIH application ID:** 11376128
- **Project number:** 7R21CA267124-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** VIKAS DUDEJA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $218,351
- **Award type:** 7
- **Project period:** 2024-06-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11376128

## Citation

> US National Institutes of Health, RePORTER application 11376128, Integrated Genomic-Transcriptomic Characterization to Identify Molecular Mechanisms of Disparities in PDAC Outcomes (7R21CA267124-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11376128. Licensed CC0.

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