Abstract
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.
Highlights
Colorectal cancer (CRC) was estimated to be the third leading component cause of cancer-related mortality in the world (Siegel et al, 2020)
The Tumor Immune Estimation Resource (TIMER) database analysis revealed that B and T lymphocyte attenuator (BTLA) mRNA expression was lower in bladder cancer (BLCA), colon adenocarcinoma (COAD), lung squamous cell carcinoma (LUSC), rectum adenocarcinoma (READ), and thyroid carcinoma (THCA) compared with adjacent normal tissues
Higher expression was observed in kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD) compared with adjacent normal tissues (Figure 1A)
Summary
Colorectal cancer (CRC) was estimated to be the third leading component cause of cancer-related mortality in the world (Siegel et al, 2020). Other effective treatments are in urgent to improve the prognosis of CRC patients. Major immunotherapy trials in metastatic CRC have been focused on selective anti- programmd death 1 (PD-1), anti-PD-L1, and anti-Cytotoxic T lymphocyte antigen 4 (CTLA-4) monoclonal antibodies. Immune checkpoint inhibitors are sure to have therapeutic effects supporting by plenty of clinical evidence, but the vast majority of patients with MMR or microsatellite stable (MSS) do not benefit from immunotherapy (Le et al, 2015; Bendell et al, 2016; Overman et al, 2018). New effective immunotherapy targets, which can make the tumor more sensitive to immune checkpoint inhibitors and lend extensive immune infiltration, are in urgent need. The role of BTLA in prognosis and immunotherapy of colorectal cancer (CRC) remains unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
