Gene variation impact on prostate cancer progression: Lymphocyte modulator, activation, and cell adhesion gene variant contribution.


Journal

The Prostate
ISSN: 1097-0045
Titre abrégé: Prostate
Pays: United States
ID NLM: 8101368

Informations de publication

Date de publication:
10 2022
Historique:
revised: 29 04 2022
received: 08 02 2022
accepted: 01 06 2022
pubmed: 30 6 2022
medline: 1 9 2022
entrez: 29 6 2022
Statut: ppublish

Résumé

The view of prostate cancer (PCa) progression as a result of the interaction of epithelial cancer cells with the host's immune system is supported by the presence of tumor infiltrating lymphocytes (TILs). TILs fate and interaction with the tumor microenvironment is mediated by accessory molecules such as CD5 and CD6, two signal-transducing coreceptors involved in fine-tuning of T cell responses. While the nature of the CD5 ligand is still controversial, CD6 binds CD166/ALCAM, a cell adhesion molecule involved in progression and dissemination of epithelial cancers, including PCa. The purpose of the present study was to determine the role of CD5, CD6, and CD166/ALCAM gene variants in PCa. Functionally relevant CD5 (rs2241002 and rs2229177), CD6 (rs17824933, rs11230563, and rs12360861) and CD166/ALCAM (rs6437585, rs579565, rs1044243, and rs35271455) single nucleotide polymorphisms (SNPs) were genotyped in germline DNA samples from 376 PCa patients. Their association with PCa prognostic factors, namely biochemical recurrence (BCR) and International Society of Urological Pathology (ISUP) grade was analyzed by generalized linear models and survival analyses. Proportional hazards regression showed that the minor CD6 rs12360861 The results show the impact on PCa aggressiveness and recurrence brought about by gene variants involved in modulation of lymphocyte activation (CD5, CD6) and immune-epithelial cell adhesion (CD166/ALCAM) in PCa aggressiveness and recurrence, thus supporting a role for host immune response in PCa pathophysiology.

Sections du résumé

BACKGROUND
The view of prostate cancer (PCa) progression as a result of the interaction of epithelial cancer cells with the host's immune system is supported by the presence of tumor infiltrating lymphocytes (TILs). TILs fate and interaction with the tumor microenvironment is mediated by accessory molecules such as CD5 and CD6, two signal-transducing coreceptors involved in fine-tuning of T cell responses. While the nature of the CD5 ligand is still controversial, CD6 binds CD166/ALCAM, a cell adhesion molecule involved in progression and dissemination of epithelial cancers, including PCa. The purpose of the present study was to determine the role of CD5, CD6, and CD166/ALCAM gene variants in PCa.
METHODS
Functionally relevant CD5 (rs2241002 and rs2229177), CD6 (rs17824933, rs11230563, and rs12360861) and CD166/ALCAM (rs6437585, rs579565, rs1044243, and rs35271455) single nucleotide polymorphisms (SNPs) were genotyped in germline DNA samples from 376 PCa patients. Their association with PCa prognostic factors, namely biochemical recurrence (BCR) and International Society of Urological Pathology (ISUP) grade was analyzed by generalized linear models and survival analyses.
RESULT
Proportional hazards regression showed that the minor CD6 rs12360861
CONCLUSION
The results show the impact on PCa aggressiveness and recurrence brought about by gene variants involved in modulation of lymphocyte activation (CD5, CD6) and immune-epithelial cell adhesion (CD166/ALCAM) in PCa aggressiveness and recurrence, thus supporting a role for host immune response in PCa pathophysiology.

Identifiants

pubmed: 35767366
doi: 10.1002/pros.24407
pmc: PMC9542726
doi:

Substances chimiques

ALCAM protein, human 0
Activated-Leukocyte Cell Adhesion Molecule 0
Antigens, CD 0
Antigens, Differentiation, T-Lymphocyte 0
CD5 Antigens 0
CD6 antigen 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1331-1337

Informations de copyright

© 2022 The Authors. The Prostate published by Wiley Periodicals LLC.

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Auteurs

Sergi Casadó-Llombart (S)

Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Tarek Ajami (T)

Laboratori i Servei d'Urologia, Hospital Clínic de Barcelona, Barcelona, Spain.

Marta Consuegra-Fernández (M)

Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Esther Carreras (E)

Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Fernando Aranda (F)

Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Noelia Armiger (N)

Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Antonio Alcaraz (A)

Laboratori i Servei d'Urologia, Hospital Clínic de Barcelona, Barcelona, Spain.
Genètica i tumors urològics, Institut d'Investigacions Biomèdiques August Pi i Sunyer, IDIBAPS, Barcelona, Spain.

Lourdes Mengual (L)

Laboratori i Servei d'Urologia, Hospital Clínic de Barcelona, Barcelona, Spain.
Genètica i tumors urològics, Institut d'Investigacions Biomèdiques August Pi i Sunyer, IDIBAPS, Barcelona, Spain.
Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain.

Francisco Lozano (F)

Immunoreceptors del Sistema Innat i Adaptatiu, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Genètica i tumors urològics, Institut d'Investigacions Biomèdiques August Pi i Sunyer, IDIBAPS, Barcelona, Spain.
Departament de Biomedicina, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain.
Servei d'Immunologia, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, Barcelona, Spain.

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