Research in Brief: Cracking the Code

First-of-Its-Kind Proteomic Study of Pancreatic Neuroendocrine Tumors May Open Door to New Therapies 

Pancreatic neuroendocrine tumors (PanNETs) are a rare form of pancreatic cancer for which predicting patient clinical outcomes and providing appropriate patient management remain challenging.

In a first-of-its-kind investigation, scientists at Beth Israel Deaconess Medical Center (BIDMC) used proteogenomics—the integrated large-scale study of genomes and proteomes—to characterize 37 pancreatic neuroendocrine tumors. The research team used the latest-generation protein mass spectrometry.

The work identified four previously undescribed PanNET subtypes. Two proteomic subtypes showed high recurrence rates, suggesting a previously unrecognized clinical aggressiveness. Hypoxia and inflammatory pathways were significantly enriched in these clinically aggressive subtypes. Detailed analyses revealed metabolic pathway adaptation and enrichment of immunosuppressive molecules that could potentially serve as therapeutic targets.

Importantly, the researchers add, these proteomic subtypes would not have been discoverable using prior genomics-based approaches to PanNETs or current state-of-the-art clinicopathological PanNET subtyping. Michael Roehrl, Chief of the Department of Pathology and PI at BIDMC said: “Proteogenomics represents a significant step forward in understanding pancreatic neuroendocrine tumors, and our publicly available proteomic PanNET dataset should be of immediate interest to scientists and physicians around the world.”

Read the full paper in iScience (a Cell family journal).

BIDMC Study Authors: Michael H. Roehrl, Atsushi Tanaka, Makiko Ogawa, Yusuke Otani

COI: Atsushi Tanaka, Makiko Ogawa and Yusuke Otani declare no conflicts of interest related to this study.  Michael H. Roehrl is a member of the Scientific Advisory Boards of Azenta Life Sciences and Universal Diagnostics (UDX). Neither of these companies had any role in the support, design, execution, data analysis, or any other aspect of this study.

Tanaka, A., Ogawa, M., Zhou, Y., Otani, Y., Hendrickson, R.C., Miele, M.M., Li, Z., Klimstra, D.S., Wang, J.Y., Roehrl, M.H., Proteogenomic characterization of pancreatic neuroendocrine tumors uncovers hypoxia and immune signatures in clinically aggressive subtypes, ISCIENCE (2024).