Belotti Yuri, Lim Su Bin, Iyer Narayanan Gopalakrishna, Lim Wan-Teck, Lim Chwee Teck
Institute for Health Innovation and Technology, National University of Singapore, 14 Medical Drive, Singapore 117599, Singapore.
Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 16499, Korea.
Cancers (Basel). 2021 Nov 17;13(22):5761. doi: 10.3390/cancers13225761.
Squamous cell carcinoma of the head and neck (SCCHN) is common worldwide and related to several risk factors including smoking, alcohol consumption, poor dentition and human papillomavirus (HPV) infection. Different etiological factors may influence the tumor microenvironment and play a role in dictating response to therapeutics. Here, we sought to investigate whether an early-stage SCCHN-specific prognostic matrisome-derived gene signature could be identified for HPV-negative SCCHN patients ( = 168), by applying a bioinformatics pipeline to the publicly available SCCHN-TCGA dataset. We identified six matrisome-derived genes with high association with prognostic outcomes in SCCHN. A six-gene risk score, the SCCHN TMI (SCCHN-tumor matrisome index: composed of MASP1, EGFL6, SFRP5, SPP1, MMP8 and P4HA1) was constructed and used to stratify patients into risk groups. Using machine learning-based deconvolution methods, we found that the risk groups were characterized by a differing abundance of infiltrating immune cells. This work highlights the key role of immune infiltration cells in the overall survival of patients affected by HPV-negative SCCHN. The identified SCCHN TMI represents a genomic tool that could potentially aid patient stratification and selection for therapy in these patients.
头颈部鳞状细胞癌(SCCHN)在全球范围内都很常见,并且与多种风险因素相关,包括吸烟、饮酒、牙齿状况不佳和人乳头瘤病毒(HPV)感染。不同的病因可能会影响肿瘤微环境,并在决定对治疗的反应中发挥作用。在此,我们试图通过对公开可用的SCCHN-TCGA数据集应用生物信息学流程,来确定是否可以为HPV阴性的SCCHN患者(n = 168)识别出一种早期SCCHN特异性的预后基质衍生基因特征。我们确定了六个与SCCHN预后结果高度相关的基质衍生基因。构建了一个六基因风险评分,即SCCHN TMI(SCCHN-肿瘤基质指数:由MASP1、EGFL6、SFRP5、SPP1、MMP8和P4HA1组成),并用于将患者分层为风险组。使用基于机器学习的反卷积方法,我们发现风险组的特征是浸润免疫细胞的丰度不同。这项工作突出了免疫浸润细胞在HPV阴性SCCHN患者总生存中的关键作用。所确定的SCCHN TMI代表了一种基因组工具,可能有助于这些患者的分层和治疗选择。