一种新型与氧化应激相关的基因标志物，可作为预测头颈部鳞状细胞癌患者预后和免疫治疗反应的指标。

A novel oxidative stress-related gene signature as an indicator of prognosis and immunotherapy responses in HNSCC.

机构信息

Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, Shandong 250299, P.R. China.

Radiotherapy Department, Shandong Second Provincial General Hospital, Shandong University, Jinan, Shandong 250299, P.R. China.

出版信息

Aging (Albany NY). 2023 Dec 28;15(24):14957-14984. doi: 10.18632/aging.205323.

PURPOSE

To identify molecular subtypes of oxidative stress-related genes in head and neck squamous cell carcinoma (HNSCC) and to construct a scoring model of oxidative stress-related genes.

METHODS

R language based scRNA-seq and bulk RNA-seq analyses were used to identify molecular isoforms of oxidative stress-related genes in HNSCC. An oxidative stress-related gene scoring (OSRS) model was constructed, which were verified through online data and immunohistochemical staining of clinical samples.

RESULTS

Using TCGA-HNSCC datasets, nine predictive genes for overall patient survival, rarely reported in previous similar studies, were screened. AREG and CES1 were identified as prognostic risk factors. CSTA, FDCSP, JCHAIN, IFFO2, PGLYRP4, SPOCK2 and SPINK6 were identified as prognostic factors. Collectively, all genes formed a prognostic risk signature model for oxidative stress in HNSCC, which were validated in GSE41613, GSE103322 and PRJEB23709 datasets. Immunohistochemical staining of SPINK6 in nasopharyngeal cancer samples validated the gene panel. Subsequent analysis indicated that subgroups of the oxidative stress prognostic signature played important roles during cellular communication, the immune microenvironment, the differential activation of transcription factors, oxidative stress and immunotherapeutic responses.

CONCLUSIONS

The risk model might predict HNSCC prognosis and immunotherapeutic responses.

目的

鉴定头颈鳞状细胞癌（HNSCC）中与氧化应激相关的基因的分子亚型，并构建氧化应激相关基因的评分模型。

方法

使用基于 R 语言的 scRNA-seq 和 bulk RNA-seq 分析来鉴定 HNSCC 中与氧化应激相关的基因的分子异构体。构建了氧化应激相关基因评分（OSRS）模型，并通过在线数据和临床样本的免疫组织化学染色进行了验证。

结果

使用 TCGA-HNSCC 数据集，筛选出了九个与总体患者生存相关的预测基因，这些基因在以前的类似研究中很少报道过。AREG 和 CES1 被确定为预后风险因素。CSTA、FDCSP、JCHAIN、IFFO2、PGLYRP4、SPOCK2 和 SPINK6 被确定为预后因素。所有这些基因共同构成了 HNSCC 中氧化应激的预后风险特征模型，在 GSE41613、GSE103322 和 PRJEB23709 数据集得到了验证。对鼻咽癌样本中 SPINK6 的免疫组织化学染色验证了该基因组合。随后的分析表明，氧化应激预后特征的亚组在细胞通讯、免疫微环境、转录因子的差异激活、氧化应激和免疫治疗反应中发挥了重要作用。