# Protein Expression Status of HTR4 and PDE4D Genes in Glial Brain Tumors Followed by the Study of Genomic Instability

## TL;DR

This study explores the protein expression of HTR4 and PDE4D genes in brain tumors and their link to genomic instability in gliomas.

## Contribution

The study identifies a modulatory signaling axis involving HTR4 and PDE4D proteins and validates genomic instability as a tool for tumor stratification.

## Key findings

- Synchronized expression of 5-HTR4 and PDE4D proteins reflects cAMP signaling pathway activity in gliomas.
- Genomic instability (MIN, CIN, and total GI) is a powerful tool for biological tumor stratification and risk assessment.
- HTR4 and PDE4D expression alone cannot independently stratify glioma patients.

## Abstract

Malignant gliomas are the most common primary tumors of the central nervous system (CNS), originating from glial cells. They account for 30% of all CNS tumors. Among them, glioblastoma (GBM) is the most common, accounting for 45% of all glial tumors, while low-grade gliomas (LGGs) account for 31.8% of all gliomas. The aim of this study was to analyze the protein-expression profile of HTR4 and PDE4D genes in patients with glioma by immunohistochemical (IHC) analysis, to determine whether some interrelationship between them exists, to correlate their expression with clinical and histopathological parameters and therapy, and to determine their impact on patients’ survival. In addition, we analyzed the level of genomic instability (GI) (microsatellite (MIN), chromosomal (CIN) and total GI) by AP-PCR, in order to understand whether it can represent a tool for biological stratification of glioma tumors and risk assessment. Our results revealed that synchronized expression of 5-HTR4 and PDE4D proteins represents a stable modulatory signaling axis of glial-tumor biology, and reflects the activity of cAMP signaling pathway, but cannot independently stratify patients. Moreover, our study confirms that the combination of MIN, CIN and total GI represents a powerful tool for biological tumor stratification, risk assessment and understanding the pathobiological spectrum of the disease.