# Integration of CSF Proteogenomics in the Diagnosis and Management of Diffuse Gliomas

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2024 · $638,804

## Abstract

Project Summary
Diffuse gliomas are the most common primary malignant adult brain tumor. Lower grade gliomas
(Grade 2) inevitably become malignant, and prognosis is fatal. Key clinical challenges include: 1)
significant intra- and inter-tumor molecular heterogeneity; and 2) limitations in current imaging
techniques for distinguishing true tumor recurrence (TTR), pseudo-progression (PP), or radiation
necrosis (RN) following surgical resection and adjuvant therapy. Direct tissue sampling is invasive
and may not capture the entire molecular landscape of the tumor. Non-invasive imaging (e.g.
MRI) fails to detect small recurrences, is limited in resolving differential diagnoses during imaging
follow-up, and does not capture tumor molecular evolution. Recently, liquid biopsy of proximal
fluids has gained popularity for systemic tumors. In gliomas, both blood and cerebrospinal fluid
(CSF) are viable sources of proximal fluids. While acquisition of blood is less invasive, the CSF
is physiologically expected to be a superior enriched reservoir for tumor-specific biomarkers.
Thus, CSF can be leveraged for more direct target identification, which can be subsequently
extended to blood assays. Most molecular analyses of glioblastoma have focused on the genome,
epigenome and transcriptome, but proteomic analyses are also required to understand tumor
functional phenotypes like response to therapy. We have conducted shotgun proteomics on as
little as 30 µL of CSF from patients with glioblastoma and primary central nervous system
lymphoma, detecting a substantial concentration of distinct and identifying differentially enriched
pathways for each tumor class. We hypothesize that integration of CSF-based
proteogenomic analyses can improve our diagnosis of DGs, refine our management during
tumor surveillance and offer insight into potential novel drug targets. We propose to conduct
a multi-center study focused on CSF, with the largest prospective cohort established to-date. This
project will validate our preliminary findings while establishing novel diagnostic proteomic
signatures based on CSF. We will also establish the first ever CSF glycoproteome in DGs, which
will be of great value for drug target development. Success in this proposal will have a significant
impact on diffuse glioma management through improving preoperative diagnostic precision and
subsequent surgical planning, enable early intervention for TTR while eliminating potentially
unnecessary surgery for RN, and establish a template for drug target discovery in future studies.

## Key facts

- **NIH application ID:** 10801783
- **Project number:** 1R01CA279357-01A1
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Alireza Mansouri
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $638,804
- **Award type:** 1
- **Project period:** 2024-07-03 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801783

## Citation

> US National Institutes of Health, RePORTER application 10801783, Integration of CSF Proteogenomics in the Diagnosis and Management of Diffuse Gliomas (1R01CA279357-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10801783. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*