Friend or Foe: Prognostic and Immunotherapy Roles of BTLA in Colorectal Cancer

BackgroundB and T lymphocyte attenuator (BTLA) is a co-signaling protein belonging to the CD28 immunoglobulin superfamily. However, the role of BTLA in prognosis and immunotherapy of colorectal cancer (CRC) remains unclear.MethodsWe evaluated the expression of BTLA via the Oncomine and the cancer ge...

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Main Authors: Jingjing Song, Lihui Wu
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-07-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fmolb.2020.00148/full
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author Jingjing Song
Jingjing Song
Lihui Wu
Lihui Wu
author_facet Jingjing Song
Jingjing Song
Lihui Wu
Lihui Wu
author_sort Jingjing Song
collection DOAJ
description BackgroundB and T lymphocyte attenuator (BTLA) is a co-signaling protein belonging to the CD28 immunoglobulin superfamily. However, the role of BTLA in prognosis and immunotherapy of colorectal cancer (CRC) remains unclear.MethodsWe evaluated the expression of BTLA via the Oncomine and the cancer genome atlas (TCGA) database. We research the outcome among different BTLA expression patients by Kaplan–Meier curve. We used the Chi-Squared test and Cox regression analysis to identify potential risk factors. Besides, the correlations between BTLA and cancer immune infiltration were investigated via CIBERSORT.ResultsVarious cohorts showed that BTLA expression was lower in CRC compared to corresponding normal tissue. Moreover, low BTLA expression was correlated with poor overall survival in TCGA cohorts and Gene Expression Omnibus cohorts (GSE29623 and GSE17536). Low BTLA expression was associated with less lymph node metastasis (p = 0.0123). In the Cox proportional hazards model, BTLA was identified as a favorable prognostic factor. Naive B cells, memory B cells, CD8 T cells, CD4 memory resting T cells, follicular helper T (Tfh) cells, monocytes, resting natural killing (NK) cells, M0 macrophages, M1 macrophages, resting mast cells, and activated mast cells were affected by BTLA expression (all p < 0.01). Correlated immune markers and functional enrichment analysis revealed BTLA functioned in the T cell receptor signaling pathway, B cell receptor signaling pathway, and NK cell-mediated cytotoxicity pathway.ConclusionThese analyses suggest BTLA is a potential factor for extended survival and closely related to CD8 T cells, Tfh cells, B cells, and NK cells in CRC. We summarize these results that BTLA can be used as a prognostic biomarker and might contribute to developing novel CRC immunological treatment strategies.
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spelling doaj.art-443042cef9384a49aea34d165bb3db1d2022-12-21T23:57:55ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2020-07-01710.3389/fmolb.2020.00148542671Friend or Foe: Prognostic and Immunotherapy Roles of BTLA in Colorectal CancerJingjing Song0Jingjing Song1Lihui Wu2Lihui Wu3Department of Children’s Health Care, The Second Affiliated Hospital & Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, ChinaDepartment of Clinical Medicine, Hangzhou Medical College, Hangzhou, ChinaDepartment of Children’s Health Care, The Second Affiliated Hospital & Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, ChinaDepartment of Clinical Medicine, Hangzhou Medical College, Hangzhou, ChinaBackgroundB and T lymphocyte attenuator (BTLA) is a co-signaling protein belonging to the CD28 immunoglobulin superfamily. However, the role of BTLA in prognosis and immunotherapy of colorectal cancer (CRC) remains unclear.MethodsWe evaluated the expression of BTLA via the Oncomine and the cancer genome atlas (TCGA) database. We research the outcome among different BTLA expression patients by Kaplan–Meier curve. We used the Chi-Squared test and Cox regression analysis to identify potential risk factors. Besides, the correlations between BTLA and cancer immune infiltration were investigated via CIBERSORT.ResultsVarious cohorts showed that BTLA expression was lower in CRC compared to corresponding normal tissue. Moreover, low BTLA expression was correlated with poor overall survival in TCGA cohorts and Gene Expression Omnibus cohorts (GSE29623 and GSE17536). Low BTLA expression was associated with less lymph node metastasis (p = 0.0123). In the Cox proportional hazards model, BTLA was identified as a favorable prognostic factor. Naive B cells, memory B cells, CD8 T cells, CD4 memory resting T cells, follicular helper T (Tfh) cells, monocytes, resting natural killing (NK) cells, M0 macrophages, M1 macrophages, resting mast cells, and activated mast cells were affected by BTLA expression (all p < 0.01). Correlated immune markers and functional enrichment analysis revealed BTLA functioned in the T cell receptor signaling pathway, B cell receptor signaling pathway, and NK cell-mediated cytotoxicity pathway.ConclusionThese analyses suggest BTLA is a potential factor for extended survival and closely related to CD8 T cells, Tfh cells, B cells, and NK cells in CRC. We summarize these results that BTLA can be used as a prognostic biomarker and might contribute to developing novel CRC immunological treatment strategies.https://www.frontiersin.org/article/10.3389/fmolb.2020.00148/fullBTLAtumor-infiltrationprognosiscolorectal cancerimmunotherapy
spellingShingle Jingjing Song
Jingjing Song
Lihui Wu
Lihui Wu
Friend or Foe: Prognostic and Immunotherapy Roles of BTLA in Colorectal Cancer
Frontiers in Molecular Biosciences
BTLA
tumor-infiltration
prognosis
colorectal cancer
immunotherapy
title Friend or Foe: Prognostic and Immunotherapy Roles of BTLA in Colorectal Cancer
title_full Friend or Foe: Prognostic and Immunotherapy Roles of BTLA in Colorectal Cancer
title_fullStr Friend or Foe: Prognostic and Immunotherapy Roles of BTLA in Colorectal Cancer
title_full_unstemmed Friend or Foe: Prognostic and Immunotherapy Roles of BTLA in Colorectal Cancer
title_short Friend or Foe: Prognostic and Immunotherapy Roles of BTLA in Colorectal Cancer
title_sort friend or foe prognostic and immunotherapy roles of btla in colorectal cancer
topic BTLA
tumor-infiltration
prognosis
colorectal cancer
immunotherapy
url https://www.frontiersin.org/article/10.3389/fmolb.2020.00148/full
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AT lihuiwu friendorfoeprognosticandimmunotherapyrolesofbtlaincolorectalcancer
AT lihuiwu friendorfoeprognosticandimmunotherapyrolesofbtlaincolorectalcancer