全面分析 BTNL9 作为与甲状腺癌免疫浸润相关的预后生物标志物。

Comprehensive analysis of BTNL9 as a prognostic biomarker correlated with immune infiltrations in thyroid cancer.

机构信息

Department of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.

出版信息

BMC Med Genomics. 2023 Oct 5;16(1):234. doi: 10.1186/s12920-023-01676-8.

DOI:10.1186/s12920-023-01676-8

PMID:37798795

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10552425/

Abstract

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.

摘要

背景

甲状腺癌（THCA）是最常见的内分泌癌，疾病复发通常与转移和致死风险相关。类粘蛋白 BTNL9 蛋白（BTNL9）是免疫球蛋白家族的一员。本研究探讨了 BTNL9 在 THCA 中的预后作用。

方法

通过对甲状腺乳头状癌（PTC）和良性甲状腺结节（BTN）组织的 H3K27ac ChIP-seq 和 RNA-seq 数据进行分析，确定了 BTNL9 的基因增强子。同时，通过实时荧光定量 RT-PCR 在 30 对原发性 THCA 和相邻正常组织中验证了 BTNL9 的表达水平。从癌症基因组图谱（TCGA）和基因型组织表达（GTEx）中获取临床病理和 RNA 测序数据，分析 BTNL9 表达与免疫细胞浸润、趋化因子/细胞因子、免疫检查点基因、临床参数和预后值之间的关系。此外，还进行了结合 BTNL9 表达和免疫细胞浸润评分的生存分析。进行了功能富集分析以研究潜在的生物学机制。Cox 回归分析用于探索独立的临床指标，并建立了包含 BTNL9 表达和临床参数的列线图模型。

结果

BTNL9 在 BTN 组织的启动子区域（chr5：181,035,673-181,047,436）和基因体（chr5：181,051,544-181,054,849）处显示出明显更强的 H3K27ac 修饰。与正常组织相比，THCA 样本中 BTNL9 的表达水平显著下调，并且与 THCA 中的不同肿瘤分期、免疫细胞浸润、趋化因子/细胞因子和免疫检查点基因密切相关。功能富集分析表明，BTNL9 参与了免疫相关和癌症相关途径。Kaplan-Meier 分析表明，BTNL9 表达水平较低与无进展生存期（PFI）较差相关。BTNL9 表达和病理分期是 THCA 中 PFI 的独立预后指标。