Identification of Treg-related prognostic molecular subtypes and individualized characteristics in clear cell renal cell carcinoma through single-cell transcriptomes and bulk RNA sequencing

Copyright © 2024 Elsevier B.V. All rights reserved..

BACKGROUND: In clear cell renal cell carcinoma (ccRCC), the role of Regulatory T cells (Treg cells) as prognostic and immunotherapy response predictors is not fully explored.

METHODS: Analyzing renal clear cell carcinoma datasets from TISCH, TCGA, and GEO, we focused on 8 prognostic Treg genes to study patient subtypes in ccRCC. We assessed Treg subtypes in relation to patient prognosis, tumor microenvironment, metabolism. Using Cox regression and principal component analysis, we devised Treg scores for individual patient characterization and explored the molecular role of C1QL1, a critical gene in the Treg model, through in vivo and in vitro studies.

RESULTS: Eight Treg-associated prognostic genes were identified, classifying ccRCC patients into cluster A and B. Cluster A patients showed poorer prognosis with distinct clinical and molecular profiles, potentially benefiting more from immunotherapy. Low Treg scores correlated with worse outcomes and clinical progression. Low scores also suggested that patients might respond better to immunotherapy and targeted therapies. In ccRCC, C1QL1 knockdown reduced tumor proliferation and invasion via NF-kb-EMT pathways and decreased Treg cell infiltration, enhancing immune efficacy.

CONCLUSIONS: The molecular subtype and Treg score in ccRCC, based on Treg cell marker genes, are crucial in personalizing ccRCC treatment and underscore C1QL1's potential as a tumor biomarker and target for immunotherapy.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:130

Enthalten in:

International immunopharmacology - 130(2024) vom: 30. März, Seite 111746

Sprache:

Englisch

Beteiligte Personen:

Weng, Kang Qiang [VerfasserIn]
Liu, Jin Yu [VerfasserIn]
Li, Hu [VerfasserIn]
She, Lin Lu [VerfasserIn]
Qiu, Jun Liang [VerfasserIn]
Qi, Hao [VerfasserIn]
Qi, Hui Yue [VerfasserIn]
Li, Yong Sheng [VerfasserIn]
Dai, Ying Bo [VerfasserIn]

Links:

Volltext

Themen:

Bulk RNA sequencing
Clear cell renal cell carcinoma
Journal Article
Molecular subtypes
Single-cell RNA sequencing
Treg cells

Anmerkungen:

Date Completed 25.03.2024

Date Revised 25.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.intimp.2024.111746

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369324099