TNFRSF13B is a potential contributor to prostate cancer

Abstract Background Immunodeficiencies are genetic diseases known to predispose an individual to cancer owing to defective immunity towards malignant cells. However, the link between immunodeficiency and prostate cancer progression remains unclear. Therefore, the aim of this study was to evaluate th...

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Main Authors: Chia-Yang Li, Shu-Pin Huang, Yei-Tsung Chen, Hsin-En Wu, Wei-Chung Cheng, Chao-Yuan Huang, Chia-Cheng Yu, Victor C. Lin, Jiun-Hung Geng, Te-Ling Lu, Bo-Ying Bao
Format: Article
Language:English
Published: BMC 2022-05-01
Series:Cancer Cell International
Subjects:
Online Access:https://doi.org/10.1186/s12935-022-02590-2
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author Chia-Yang Li
Shu-Pin Huang
Yei-Tsung Chen
Hsin-En Wu
Wei-Chung Cheng
Chao-Yuan Huang
Chia-Cheng Yu
Victor C. Lin
Jiun-Hung Geng
Te-Ling Lu
Bo-Ying Bao
author_facet Chia-Yang Li
Shu-Pin Huang
Yei-Tsung Chen
Hsin-En Wu
Wei-Chung Cheng
Chao-Yuan Huang
Chia-Cheng Yu
Victor C. Lin
Jiun-Hung Geng
Te-Ling Lu
Bo-Ying Bao
author_sort Chia-Yang Li
collection DOAJ
description Abstract Background Immunodeficiencies are genetic diseases known to predispose an individual to cancer owing to defective immunity towards malignant cells. However, the link between immunodeficiency and prostate cancer progression remains unclear. Therefore, the aim of this study was to evaluate the effects of common genetic variants among eight immunodeficiency pathway-related genes on disease recurrence in prostate cancer patients treated with radical prostatectomy. Methods Genetic and bioinformatic analyses on 19 haplotype-tagging single-nucleotide polymorphisms in eight immunodeficiency pathway-related genes were conducted in 458 patients with prostate cancer after receiving radical prostatectomy. Furthermore, the TNFRSF13B was knocked down in 22Rv1 and PC-3 human prostate cancer cell lines via transfecting short hairpin RNAs and cell proliferation and colony formation assays were performed. The molecular mechanisms underlying the effects of TNFRSF13B were further explored by microarray gene expression profiling. Results TNFRSF13B rs4792800 was found to be significantly associated with biochemical recurrence even after adjustment for clinical predictors and false discovery rate correction (adjusted hazard ratio 1.78, 95% confidence interval 1.16–2.71, p = 0.008), and the G allele was associated with higher TNFRSF13B expression (p = 0.038). Increased TNFRSF13B expression suggested poor prognosis in four independent prostate cancer datasets. Furthermore, silencing TNFRSF13B expression resulted in decreased colony formation of 22Rv1 and PC-3 cells through modulating the cell cycle and p53 signalling pathways. Conclusions The present study suggests the potential role of immunodeficiency pathway-related genes, primarily TNFRSF13B, in prostate cancer progression.
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spelling doaj.art-080068cd54a84ba59a98eb5f40e9c63f2022-12-22T00:19:31ZengBMCCancer Cell International1475-28672022-05-0122111210.1186/s12935-022-02590-2TNFRSF13B is a potential contributor to prostate cancerChia-Yang Li0Shu-Pin Huang1Yei-Tsung Chen2Hsin-En Wu3Wei-Chung Cheng4Chao-Yuan Huang5Chia-Cheng Yu6Victor C. Lin7Jiun-Hung Geng8Te-Ling Lu9Bo-Ying Bao10Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical UniversityDepartment of Urology, Kaohsiung Medical University HospitalDepartment of Life Sciences, Institute of Genome Sciences, National Yang Ming Chiao Tung UniversityGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical UniversityGraduate Institute of Biomedical Science, China Medical UniversityDepartment of Urology, College of Medicine, National Taiwan University Hospital, National Taiwan UniversityDivision of Urology, Department of Surgery, Kaohsiung Veterans General HospitalDepartment of Urology, E-Da HospitalDepartment of Urology, Kaohsiung Medical University HospitalDepartment of Pharmacy, China Medical UniversityDepartment of Pharmacy, China Medical UniversityAbstract Background Immunodeficiencies are genetic diseases known to predispose an individual to cancer owing to defective immunity towards malignant cells. However, the link between immunodeficiency and prostate cancer progression remains unclear. Therefore, the aim of this study was to evaluate the effects of common genetic variants among eight immunodeficiency pathway-related genes on disease recurrence in prostate cancer patients treated with radical prostatectomy. Methods Genetic and bioinformatic analyses on 19 haplotype-tagging single-nucleotide polymorphisms in eight immunodeficiency pathway-related genes were conducted in 458 patients with prostate cancer after receiving radical prostatectomy. Furthermore, the TNFRSF13B was knocked down in 22Rv1 and PC-3 human prostate cancer cell lines via transfecting short hairpin RNAs and cell proliferation and colony formation assays were performed. The molecular mechanisms underlying the effects of TNFRSF13B were further explored by microarray gene expression profiling. Results TNFRSF13B rs4792800 was found to be significantly associated with biochemical recurrence even after adjustment for clinical predictors and false discovery rate correction (adjusted hazard ratio 1.78, 95% confidence interval 1.16–2.71, p = 0.008), and the G allele was associated with higher TNFRSF13B expression (p = 0.038). Increased TNFRSF13B expression suggested poor prognosis in four independent prostate cancer datasets. Furthermore, silencing TNFRSF13B expression resulted in decreased colony formation of 22Rv1 and PC-3 cells through modulating the cell cycle and p53 signalling pathways. Conclusions The present study suggests the potential role of immunodeficiency pathway-related genes, primarily TNFRSF13B, in prostate cancer progression.https://doi.org/10.1186/s12935-022-02590-2ImmunodeficiencyProstate cancerTNFRSF13BBiochemical recurrencePrognosisBiomarker
spellingShingle Chia-Yang Li
Shu-Pin Huang
Yei-Tsung Chen
Hsin-En Wu
Wei-Chung Cheng
Chao-Yuan Huang
Chia-Cheng Yu
Victor C. Lin
Jiun-Hung Geng
Te-Ling Lu
Bo-Ying Bao
TNFRSF13B is a potential contributor to prostate cancer
Cancer Cell International
Immunodeficiency
Prostate cancer
TNFRSF13B
Biochemical recurrence
Prognosis
Biomarker
title TNFRSF13B is a potential contributor to prostate cancer
title_full TNFRSF13B is a potential contributor to prostate cancer
title_fullStr TNFRSF13B is a potential contributor to prostate cancer
title_full_unstemmed TNFRSF13B is a potential contributor to prostate cancer
title_short TNFRSF13B is a potential contributor to prostate cancer
title_sort tnfrsf13b is a potential contributor to prostate cancer
topic Immunodeficiency
Prostate cancer
TNFRSF13B
Biochemical recurrence
Prognosis
Biomarker
url https://doi.org/10.1186/s12935-022-02590-2
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