The Expression of Alamandine Receptor MrgD in Clear Cell Renal Cell Carcinoma Is Associated with a Worse Prognosis and Unfavorable Response to Antiangiogenic Therapy

Renal cell carcinoma (RCC) ranks among the most prevalent malignancies in Western countries, marked by its notable heterogeneity, which contributes to an unpredictable clinical trajectory. The insufficiency of dependable biomarkers adds complexity to assessing this tumor progression. Imbalances of several components of the intrarenal renin-angiotensin system (iRAS) significantly impact patient prognoses and responses to first-line immunotherapies. In this study, we analyzed the immunohistochemical expression of the Mas-related G-protein-coupled receptor D (MrgD), which recognizes the novel RAS peptide alamandine (ALA), in a series of 87 clear cell renal cell (CCRCCs), 19 papillary (PRCC), 7 chromophobe (ChRCC) renal cell carcinomas, and 11 renal oncocytomas (RO). MrgD was expressed in all the renal tumor subtypes, with a higher mean staining intensity in the PRCCs, ChRCCs, and ROs. A high expression of MrgD at the tumor center and at the infiltrative front of CCRCC tissues was significantly associated with a high histological grade, large tumor diameter, local invasion, and locoregional node and distant metastasis. Patients with worse 5-year cancer-specific survival and a poorer response to antiangiogenic tyrosine-kinase inhibitors (TKIs) showed higher MrgD expression at the center of their primary tumors. These findings suggest a possible role of MrgD in renal carcinogenetic processes. Further studies are necessary to unveil its potential as a novel biomarker for CCRCC prognosis and response to frontline therapies.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:25

Enthalten in:

International journal of molecular sciences - 25(2024), 3 vom: 25. Jan.

Sprache:

Englisch

Beteiligte Personen:

Larrinaga, Gorka [VerfasserIn]
Valdivia, Asier [VerfasserIn]
Arrieta-Aguirre, Inés [VerfasserIn]
Solano-Iturri, Jon Danel [VerfasserIn]
Ugalde-Olano, Aitziber [VerfasserIn]
Loizaga-Iriarte, Ana [VerfasserIn]
Santos-Martín, Aida [VerfasserIn]
Pérez-Fernández, Amparo [VerfasserIn]
Angulo, Javier C [VerfasserIn]
López, José I [VerfasserIn]

Links:

Volltext

Themen:

Alamandine
Carrier Proteins
Journal Article
MRGPRD protein, human
MrgD receptor
Oligopeptides
Prognosis
Receptors, G-Protein-Coupled
Renal cell carcinoma
Renin–angiotensin system

Anmerkungen:

Date Completed 22.02.2024

Date Revised 22.02.2024

published: Electronic

Citation Status MEDLINE

doi:

10.3390/ijms25031499

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM368282708