Department of Biomedical Science and Technology, Graduate School, Kyung Hee University, Seoul, Republic of Korea.
Department of Otolaryngology-Head and Neck Surgery, Kyung Hee University Medical Center, Seoul, Republic of Korea.
Cancer Genomics Proteomics. 2022 Sep-Oct;19(5):591-605. doi: 10.21873/cgp.20344.
BACKGROUND/AIM: Head and neck squamous cell carcinoma (HNSCC) has poor prognosis, with survival rates that have not significantly improved over the past several decades. Therefore, prediction of HNSCC prognosis is of clinical importance. Baculoviral IAP Repeat containing 2 (BIRC2) and Baculoviral IAP Repeat containing 3 (BIRC3) are involved in oncogenic activity by modulating cell proliferation, apoptosis and invasion in HNSCC. This study aimed to develop and validate a predictive gene signature for BIRC2 and BIRC3.
The genomic copy number and gene expression for BIRC2 and BIRC3 were systematically explored in patients with HNSCC to investigate the clinical relevance of BIRC2 and BIRC3 activation. A prognostic signature was developed based on correlations associated with BIRC2 and BIRC3 mRNA expression and copy number alterations. Hierarchical clustering was used to classify the clusters (Clusters 1 and 2). Moreover, independent validation of the BIRC2-BIRC3 gene signature was performed using the Leipzig, MDACC, FHCRC, and KHU datasets. To explore the biological functions of the BIRC2-BIRC3 gene signature, string analysis and pathway annotation were also performed.
BIRC2-BIRC3 gene signature-derived cluster 2 patients exhibited significantly poor survival. This signature also predicted survival in three independent cohorts. Interestingly, the BIRC2-BIRC3 gene signature additionally permitted the identification of survival in advanced tumor stages with excellent accuracy in all three cohorts. Multivariate Cox regression analysis identified that the BIRC2-BIRC3 signature was an independent predictor associated with the survival of patients with HNSCC. Moreover, Inhibition of BIRC2 modulated the NF-B signaling pathway via upregulation of CBR1 expression.
The BIRC2-BIRC3 gene signature was found to be associated with the prognosis of HNSCC. Thus, BIRC2 and BIRC3 could be potential targets for improving HNSCC prognosis.
背景/目的：头颈部鳞状细胞癌（HNSCC）预后较差，过去几十年生存率没有显著提高。因此，预测 HNSCC 的预后具有重要的临床意义。杆状病毒 IAP 重复序列 2（BIRC2）和杆状病毒 IAP 重复序列 3（BIRC3）通过调节 HNSCC 中的细胞增殖、凋亡和侵袭参与致癌活性。本研究旨在开发和验证用于预测 BIRC2 和 BIRC3 的基因特征。
系统地研究了 HNSCC 患者中 BIRC2 和 BIRC3 的基因组拷贝数和基因表达，以研究 BIRC2 和 BIRC3 激活的临床相关性。基于与 BIRC2 和 BIRC3 mRNA 表达和拷贝数改变相关的相关性，开发了一个预后特征。使用层次聚类对聚类（聚类 1 和聚类 2）进行分类。此外，还使用莱比锡、MDACC、FHCRC 和 KHU 数据集对 BIRC2-BIRC3 基因特征进行了独立验证。为了探讨 BIRC2-BIRC3 基因特征的生物学功能，还进行了字符串分析和途径注释。
BIRC2-BIRC3 基因特征衍生的聚类 2 患者的生存明显较差。该特征还预测了三个独立队列的生存情况。有趣的是，BIRC2-BIRC3 基因特征还可以识别所有三个队列中晚期肿瘤阶段的生存情况，具有出色的准确性。多变量 Cox 回归分析确定 BIRC2-BIRC3 特征是与 HNSCC 患者生存相关的独立预测因子。此外，BIRC2 的抑制通过上调 CBR1 表达调节 NF-B 信号通路。
发现 BIRC2-BIRC3 基因特征与 HNSCC 的预后相关。因此，BIRC2 和 BIRC3 可能是改善 HNSCC 预后的潜在靶点。
