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Comprehensive analysis of BTNL9 as a prognostic biomarker correlated with immune infiltrations in thyroid cancer
BACKGROUND: Thyroid cancer (THCA) is the most common type of endocrine cancers, and the disease recurrences were usually associated with the risks of metastasis and fatality. Butyrophilin-like protein 9 (BTNL9) is a member of the immunoglobulin families. This study investigated the prognostic role o...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552425/ https://www.ncbi.nlm.nih.gov/pubmed/37798795 http://dx.doi.org/10.1186/s12920-023-01676-8 |
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author | Zhang, Luyao Yu, Shuang Hong, Shubin Xiao, Xi Liao, Zhihong Li, Yanbing Xiao, Haipeng |
author_facet | Zhang, Luyao Yu, Shuang Hong, Shubin Xiao, Xi Liao, Zhihong Li, Yanbing Xiao, Haipeng |
author_sort | Zhang, Luyao |
collection | PubMed |
description | BACKGROUND: Thyroid cancer (THCA) is the most common type of endocrine cancers, and the disease recurrences were usually associated with the risks of metastasis and fatality. Butyrophilin-like protein 9 (BTNL9) is a member of the immunoglobulin families. This study investigated the prognostic role of BTNL9 in THCA. METHODS: Gene enhancers of BTNL9 were identified by interrogating H3K27ac ChIP-seq and RNA-seq data of papillary thyroid cancer (PTC) and benign thyroid nodule (BTN) tissues. Meanwhile, BTNL9 expression level was verified by qRT-PCR in 30 pairs of primary THCA and adjacent normal tissues. Clinicopathological and RNA sequencing data were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) to analyze the relations between BTNL9 expression and immune cell infiltration, chemokines/cytokines, immune checkpoint genes, clinical parameters and prognosis values. Besides, survival analysis combining BTNL9 expression and immune cell infiltration scores was conducted. Functional enrichment analysis was performed to investigate the potential biological mechanisms. Cox regression analyses were used to explore independent clinical indicators, and a nomogram model incorporating BTNL9 expression with clinical parameters was established. RESULTS: BTNL9 showed significantly stronger H3K27ac modifications in BTN than PTC tissues at the promoter region (chr5: 181,035,673–181,047,436) and gene body (chr5: 181,051,544–181,054,849). The expression levels of BTNL9 were significantly down-regulated in THCA samples compared to normal tissues, and were strongly associated with different tumor stages, immune cell infiltrations, chemokines/cytokines and immune checkpoint genes in THCA. Functional enrichment analyses indicated that BTNL9 was involved in immune-related and cancer-related pathways. The Kaplan–Meier analysis showed lower BTNL9 expression was associated with poorer progression-free interval (PFI). BTNL9 expression and pathologic stages were independent prognostic indicators of PFI in THCA. CONCLUSIONS: The results implied an important role of BTNL9 in the tumor progression, with the possibility of serving as a novel prognostic biomarker and a potential therapeutic target for THCA. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-023-01676-8. |
format | Online Article Text |
id | pubmed-10552425 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-105524252023-10-06 Comprehensive analysis of BTNL9 as a prognostic biomarker correlated with immune infiltrations in thyroid cancer Zhang, Luyao Yu, Shuang Hong, Shubin Xiao, Xi Liao, Zhihong Li, Yanbing Xiao, Haipeng BMC Med Genomics Research BACKGROUND: Thyroid cancer (THCA) is the most common type of endocrine cancers, and the disease recurrences were usually associated with the risks of metastasis and fatality. Butyrophilin-like protein 9 (BTNL9) is a member of the immunoglobulin families. This study investigated the prognostic role of BTNL9 in THCA. METHODS: Gene enhancers of BTNL9 were identified by interrogating H3K27ac ChIP-seq and RNA-seq data of papillary thyroid cancer (PTC) and benign thyroid nodule (BTN) tissues. Meanwhile, BTNL9 expression level was verified by qRT-PCR in 30 pairs of primary THCA and adjacent normal tissues. Clinicopathological and RNA sequencing data were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) to analyze the relations between BTNL9 expression and immune cell infiltration, chemokines/cytokines, immune checkpoint genes, clinical parameters and prognosis values. Besides, survival analysis combining BTNL9 expression and immune cell infiltration scores was conducted. Functional enrichment analysis was performed to investigate the potential biological mechanisms. Cox regression analyses were used to explore independent clinical indicators, and a nomogram model incorporating BTNL9 expression with clinical parameters was established. RESULTS: BTNL9 showed significantly stronger H3K27ac modifications in BTN than PTC tissues at the promoter region (chr5: 181,035,673–181,047,436) and gene body (chr5: 181,051,544–181,054,849). The expression levels of BTNL9 were significantly down-regulated in THCA samples compared to normal tissues, and were strongly associated with different tumor stages, immune cell infiltrations, chemokines/cytokines and immune checkpoint genes in THCA. Functional enrichment analyses indicated that BTNL9 was involved in immune-related and cancer-related pathways. The Kaplan–Meier analysis showed lower BTNL9 expression was associated with poorer progression-free interval (PFI). BTNL9 expression and pathologic stages were independent prognostic indicators of PFI in THCA. CONCLUSIONS: The results implied an important role of BTNL9 in the tumor progression, with the possibility of serving as a novel prognostic biomarker and a potential therapeutic target for THCA. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-023-01676-8. BioMed Central 2023-10-05 /pmc/articles/PMC10552425/ /pubmed/37798795 http://dx.doi.org/10.1186/s12920-023-01676-8 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Zhang, Luyao Yu, Shuang Hong, Shubin Xiao, Xi Liao, Zhihong Li, Yanbing Xiao, Haipeng Comprehensive analysis of BTNL9 as a prognostic biomarker correlated with immune infiltrations in thyroid cancer |
title | Comprehensive analysis of BTNL9 as a prognostic biomarker correlated with immune infiltrations in thyroid cancer |
title_full | Comprehensive analysis of BTNL9 as a prognostic biomarker correlated with immune infiltrations in thyroid cancer |
title_fullStr | Comprehensive analysis of BTNL9 as a prognostic biomarker correlated with immune infiltrations in thyroid cancer |
title_full_unstemmed | Comprehensive analysis of BTNL9 as a prognostic biomarker correlated with immune infiltrations in thyroid cancer |
title_short | Comprehensive analysis of BTNL9 as a prognostic biomarker correlated with immune infiltrations in thyroid cancer |
title_sort | comprehensive analysis of btnl9 as a prognostic biomarker correlated with immune infiltrations in thyroid cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10552425/ https://www.ncbi.nlm.nih.gov/pubmed/37798795 http://dx.doi.org/10.1186/s12920-023-01676-8 |
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