Wusiman Dilinaer, Li Wenbin, Guo Lei, Huang Zehao, Zhang Yi, Zhang Xiwei, Zhao Xiaohui, Li Lin, An Zhaohong, Li Zhengjiang, Ying Jianming, An Changming
Department of Head and Neck Surgery, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Department of Pathology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Heliyon. 2023 Nov 24;9(12):e22656. doi: 10.1016/j.heliyon.2023.e22656. eCollection 2023 Dec.
Recent studies have shown that B cells and the associated tertiary lymphoid structures (TLS) correlate with the response of patients to immune checkpoint inhibitors (ICIs) and predict overall survival (OS) in cancer patients. We screened 145 B cell marker genes (BCMG) by a comprehensive analysis of single-cell RNA-sequencing (scRNA-seq) data of head and neck squamous cell carcinoma (HNSC) from the Gene Expression Omnibus (GEO) database. The BCMG signature (BCMGS) was established using The Cancer Genome Atlas (TCGA) dataset of HNSC and verified in four independent datasets. The multivariate Cox regression analysis identified the signature as an independent prognostic factor. A prognostic nomogram was constructed with independent prognostic factors using the TCGA dataset. GO and KEGG analysis revealed the underlying signaling pathways related to this signature. Study of immune profiles showed that patients in the low-risk group presented discriminative immune-cell infiltrations. Furthermore, the low-risk group was featured by higher TCR and BCR diversity, which suggested that low-risk patients may be more sensitive to ICIs. Immunohistochemistry was performed, and we found that high expression of FTH1 was significantly correlated with poor OS ( = 0.025). The expression of TIM-3, LAG-3 and PD-1 was positively correlated and associated with better OS in HNSC. However, there was no statistically significant difference between PD-L1, PD-L2, CTLA-4, TIGIT and prognosis. The BCMGS was a promising prognostic biomarker in HNSC, which may help to interpret the responses to immunotherapy and provide a new perspective for future research on the treatment in HNSC.
最近的研究表明，B细胞及相关的三级淋巴结构（TLS）与患者对免疫检查点抑制剂（ICI）的反应相关，并可预测癌症患者的总生存期（OS）。我们通过对基因表达综合数据库（GEO）中头颈部鳞状细胞癌（HNSC）的单细胞RNA测序（scRNA-seq）数据进行全面分析，筛选了145个B细胞标志物基因（BCMG）。利用HNSC的癌症基因组图谱（TCGA）数据集建立了BCMG特征（BCMGS），并在四个独立数据集中进行了验证。多变量Cox回归分析确定该特征为独立的预后因素。使用TCGA数据集构建了包含独立预后因素的预后列线图。基因本体（GO）和京都基因与基因组百科全书（KEGG）分析揭示了与该特征相关的潜在信号通路。免疫图谱研究表明，低风险组患者存在有区别的免疫细胞浸润。此外，低风险组的特点是TCR和BCR多样性更高，这表明低风险患者可能对ICI更敏感。进行了免疫组织化学检测，我们发现FTH1的高表达与较差的OS显著相关（P = 0.025）。在HNSC中，TIM-3、LAG-3和PD-1的表达呈正相关且与较好的OS相关。然而，PD-L1、PD-L2、CTLA-4、TIGIT与预后之间无统计学显著差异。BCMGS是HNSC中一个有前景的预后生物标志物，可以帮助解释免疫治疗反应，并为HNSC未来的治疗研究提供新的视角。
