# Proteomic Characterization of Pancreatic Neuroendocrine Tumors and Metastatic Progression

> **NIH NIH R21** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2022 · $218,824

## Abstract

Project Summary/Abstract
Patients with seemingly identical pancreatic neuroendocrine tumors (PanNETs) often differ in their clinical outcomes
(emergence of metastases, treatment response, survival, etc.), suggesting that these malignancies may in fact be of different
subtypes that are currently unknown and indistinguishable by standard diagnostics (e.g., histology or genomics). PanNETs
have been difficult to further classify or risk-stratify by traditional genomic or transcriptomic methods alone. Currently,
follow-up monitoring after surgical resection is mostly based on radiographic imaging alone. There are no curative therapies
once metastases occur, no protein markers of early detection and metastatic risk, and no established molecular means of
surveillance. We hypothesize that PanNETs can be better classified according to proteome signatures. We propose to
uncover new proteome-based subtypes by deep proteomic analysis that better define these tumors.
In preliminary studies, we have shown that proteomic profiling can distinguish and sub-classify various tumors and identify
protein signatures characteristic of primary or metastatic lesions. In this proposal, we will first elucidate the deep proteomes
of well differentiated PanNETs of histologic grades ranging from G1 to G3. We will study tissues from two clinical outcome
cohorts, a “low risk” group (tumors did not show metastases for at least 5 years after surgery) and a “high risk” group
(tumors developed subsequent metastases, but are otherwise indistinguishable by current diagnostic means). By examining
both primary and metastatic lesions, we will identify protein markers that differentiate these two outcomes and signatures
that distinguish primary from metastatic lesions. Spatial heterogeneity within and between tumors, neopeptide/neoprotein
markers, and phosphoproteomic signaling pathways will also be examined. Extensive proteomic and integrated
proteogenomic analyses will be performed to define proteome-based subtypes within PanNETs and between primary and
metastatic lesions. We will validate marker panels in independent cohorts by immunohistochemistry and correlate with
clinical outcomes. Based on the protein-panel signatures, we will be able to develop risk stratification models that predict
metastatic propensity of PanNETs.
Our study will have significant impact on understanding pancreatic neuroendocrine tumors. The likelihood of success of
this proposal is high, as we have already discovered new cancer subtypes in our preliminary studies. The project will benefit
from the strong scientific and clinical expertise of the project team and the high volume of rare pancreatic neoplasms treated
at MSKCC. Our envisioned proteome-based risk stratification may explain the clinical conundrum of why patients with
currently seemingly similar PanNETs exhibit strikingly different metastatic propensity, treatment response, and length of
survival. New proteomic subtyping may inform future therapy deve...

## Key facts

- **NIH application ID:** 10907222
- **Project number:** 7R21CA263262-03
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Michael H. A. Roehrl
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $218,824
- **Award type:** 7
- **Project period:** 2021-08-20 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907222

## Citation

> US National Institutes of Health, RePORTER application 10907222, Proteomic Characterization of Pancreatic Neuroendocrine Tumors and Metastatic Progression (7R21CA263262-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10907222. Licensed CC0.

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