Comprehensive analysis of PDE2A: a novel biomarker for prognostic value and immunotherapeutic potential in human cancers

Sep 21, 2026

Phosphodiesterase 2A (PDE2A) modulates cyclic nucleotide metabolism and has been linked to multiple tumors, yet its expression patterns, prognostic impact, and immune roles across cancer types remain insufficiently defined. Using bioinformatics, the study comprehensively analyzed PDE2A gene expression in diverse human cancers and found marked reductions versus normal tissues. PDE2A levels correlated with prognosis in multiple cancers and acted as an independent prognostic factor, with decreased DNA methylation, predominant amplifications, associations with immune checkpoint genes, tumor mutation burden, microsatellite instability, single-cell functions in differentiation and angiogenesis, enrichment in synaptic transmission and tumor development, and drug sensitivity changes.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Abstract

Introduction

Material and Methods

Gene expression analysis

Brazilian Journal of Medical and Biological Research (2024) 57: e14220, [https://doi.org/10.1590/1414-431X2024e14220](https://doi.org/10.1590/1414-431X2024e14220) ISSN 1414-431X Research Article 1/17 Comprehensive analysis of PDE2A: a novel biomarker for prognostic value and immunotherapeutic potential in human cancers Zhen Yu 1* 00 , Yawen Song 1* 00 , Jin Wang 1,2 00 , Yujing Wu1 00 , Hefang Wang3 00 , Shuye Liu 1 00 , and Yu Zhu 1 00 1Nankai University Afﬁnity the Third Central Hospital, Tianjin Third Central Hospital, Tianjin, China 2Qingpu Branch of Zhongshan Hospital Afﬁliated to Fudan University, Shanghai, China 3College of Chemistry, Nankai University, Tianjin, China Abstract Phosphodiesterase 2A (PDE2A) plays a pivotal role in modulating cyclic nucleotide metabolism. Recent studies have shown that PDE2A is associated with some tumors, but its expression proﬁles, prognostic signiﬁcance, and immunological roles in diverse cancer types remain unclear. Utilizing advanced bioinformatics tools, we performed a comprehensive analysis of PDE2A gene expression in multiple human cancers. Our study revealed that PDE2A expression was signiﬁcantly reduced in the majority of cancer types and clinicopathological stages (I to IV) compared to normal tissues. Additionally, PDE2A expression was closely related to the prognosis of cancers such as stomach adenocarcinoma (STAD), ovarian serous cystadenocarcinoma (OV), and liver hepatocellular carcinoma (LIHC) . Cox regression analyses indicated that PDE2A can act as an independent prognostic factor for these cancers. The level of PDE2A DNA methylation was signiﬁcantly decreased in most cancers. Genetic alterations in PDE2A predominantly manifest in the form of ampliﬁcations. Moreover, inﬁltrating cells and immune checkpoint genes, including PDCD1, exhibited notable correlations with PDE2A expression. Signiﬁcant associations were observed between PDE2A expression and tumor mutation burden as well as microsatellite instability. Single cell sequencing revealed PDE2A ’s crucial role in regulating differentiation and angiogenesis of cancer cells. Functional enrichment analysis emphasized the important role of PDE2A in synaptic transmission and tumor development. Aberrant expression of PDE2A inﬂuenced the sensitivity of various antitumor and chemotherapy drugs. This research provided a comprehensive analysis of PDE2A in human cancers, highlighting its potential as both a prognostic marker and an immunotherapy target for future research. Key words: Phosphodiesterase 2A (PDE2A); Comprehensive analysis; Gene expression; Prognostic marker; Immunotherapy target Introduction Cancer, a multifaceted and heterogeneous disease, profoundly impacts human health and quality of life (1) . In recent years, pan-cancer analysis has emerged as a valuable approach for exploring innovative tumor therapies (2) . It involves comprehensive studies encompassing multiple cancer types to identify the commonalities and differences in their genetic, epigenetic, and molecular characteristic (3) . This analysis has the potential to reveal new biomarkers and therapeutic targets, paving the way for more personalized and effective cancer treatment. Phosphodiesterase 2A (PDE2A) is a member of thephosphodiesterases (PDEs) superfamily (4) . PDEs are a diverse group of enzymes that regulate cellular signaling by modulating cyclic nucleotide levels (5) . PDE2Aspeciﬁcally hydrolyzes cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), thereby inﬂuencing important intracellular signaling pathways (6) . Aberrant expression or activity of PDE2A has been associated with the dysregulation of cellular processes such as proliferation, migration, invasion, and angiogenesis, which are pivotal hallmarks of cancer progression (7–10) . Chen et al. (7) found that overexpression of PDE2A could inhibit the proliferation, colony formation, migration, and invasion of hepatocellular carcinoma c

FAQs

What was the main objective of the study on PDE2A?

To perform a comprehensive pan-cancer analysis of PDE2A expression and connect expression differences with clinical features, prognosis, genetic alterations, immune functions, and drug sensitivity.

How does PDE2A expression differ between cancers and normal tissues?

PDE2A expression was significantly reduced in most cancer types and across clinicopathological stages I to IV compared with normal tissues.

What relationships did the study find between PDE2A and the tumor immune environment?

PDE2A expression showed notable correlations with infiltrating cells and immune checkpoint genes, including PDCD1, and was also associated with tumor mutation burden and microsatellite instability.

Sep 21, 2026

Uploaded by Clementine