Department of Otorhinolaryngology Head & Neck Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
PLoS One. 2022 Jun 2;17(6):e0269166. doi: 10.1371/journal.pone.0269166. eCollection 2022.
In the current study, we aimed to investigate the expression of the five microsomal signal peptidase complex (SPC) subunit genes (SEC11A, SEC11C, SPCS1, SPCS2, and SPCS3) in head and neck squamous cell carcinoma (HNSC) and to explore their prognostic value. Data from the HNSC subset of The Cancer Genome Atlas (TCGA) and one previous single-cell RNA-seq dataset was used. Subgroup analysis was conducted in tumors from different anatomic sites. Gene set enrichment analysis (GSEA), and immune cell infiltration analysis were performed to check the influence of SEC11A on the tumor microenvironment. Among the genes significantly upregulated in the tumor group, only SEC11A expression (as a continuous variable) is independently associated with poorer progression-free survival (PFS) (HR: 2.075, 95%CI: 1.447-2.977, p<0.001) and disease-specific survival (DSS) (HR: 2.023, 95%CI: 1.284-3.187, p = 0.002). Subgroup analysis confirmed the prognostic value in tumors from three anatomic origins, including laryngeal squamous cell carcinoma, oral cavity-related squamous cell carcinoma, and oropharynx-related squamous cell carcinoma. SEC11A is expressed in all subtypes of cells in the tumor microenvironment. Its expression showed a moderate positive correlation with its gene-level copy number (Pearson's r = 0.53, p<0.001). SEC11A expression was negatively correlated with CD8+ T cells and B cells, but was positively correlated with cancer-associated fibroblast and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. In summary, SEC11A upregulation is a result of gene amplification in head and neck squamous cell carcinoma. Its upregulation might serve as an independent prognostic biomarker and a predictor of the infiltration of certain types of immune cells.
在本研究中，我们旨在研究五重微粒体信号肽酶复合物（SPC）亚基基因（SEC11A、SEC11C、SPCS1、SPCS2 和 SPCS3）在头颈部鳞状细胞癌（HNSC）中的表达，并探讨其预后价值。使用了来自 HNSC 子集中的癌症基因组图谱（TCGA）和一个之前的单细胞 RNA-seq 数据集的数据。对来自不同解剖部位的肿瘤进行了亚组分析。进行了基因集富集分析（GSEA）和免疫细胞浸润分析，以检查 SEC11A 对肿瘤微环境的影响。在肿瘤组中显著上调的基因中，只有 SEC11A 表达（作为连续变量）与较差的无进展生存期（PFS）（HR：2.075，95%CI：1.447-2.977，p<0.001）和疾病特异性生存（DSS）（HR：2.023，95%CI：1.284-3.187，p=0.002）独立相关。亚组分析证实了来自三个解剖起源的肿瘤的预后价值，包括喉鳞状细胞癌、口腔相关鳞状细胞癌和口咽相关鳞状细胞癌。SEC11A 在肿瘤微环境中的所有细胞亚型中均有表达。其表达与基因水平拷贝数呈中度正相关（Pearson's r=0.53，p<0.001）。SEC11A 表达与 CD8+T 细胞和 B 细胞呈负相关，但与肿瘤微环境中的癌症相关成纤维细胞和髓系来源抑制细胞（MDSCs）呈正相关。总之，SEC11A 的上调是头颈部鳞状细胞癌中基因扩增的结果。其上调可能是独立的预后生物标志物，并可预测某些类型免疫细胞的浸润。
