Department of Otolaryngology Head and Neck Surgery, Ningbo Medical Center Lihuili Hospital, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, China.
School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
BMC Bioinformatics. 2023 Jun 29;24(1):269. doi: 10.1186/s12859-023-05399-6.
This study aims to explore the predictive value of SLC25A17 in the prognosis and tumor microenvironment (TME) of patients with head and neck squamous cell carcinoma (HNSCC) and to provide ideas for individual clinical treatment.
A pancancer analysis of the differential expression of SLC25A17 among different tumors was first conducted via the TIMER 2.0 database. Subsequently, the expression of SLC25A17 and related clinical information of HNSCC patients were obtained from the TCGA database, and patients were divided into two groups according to the median value of SLC25A17 expression. K‒M survival analysis was conducted to compare the overall survival (OS) and progression-free survival (PFS) between the groups. The Wilcoxon test was used to compare the distribution of SLC25A17 in different clinical characteristics, and univariate Cox and multivariate Cox analyses were performed to analyze independent prognostic factors to establish a predictive nomogram. Calibration curves were generated to verify the reliability of predicting 1-year, 3-year and 5-year survival rates and another cohort (GSE65858) was used for external validation. Gene set enrichment analysis was conducted to compare the enriched pathways, and the immune microenvironment was assessed using the CIBERSORT and estimate packages. Furthermore, the expression levels of SLC25A17 in immune cells were also analyzed with single-cell RNA-seq via the TISCH. Moreover, the immunotherapeutic response and chemotherapy drug sensitivity were compared between the two groups to guide precise treatment. The TIDE database was applied to predict the possibility of immune escape in the TCGA-HNSC cohort.
Compared with normal samples, the expression of SLC25A17 was much higher in HNSCC tumor samples. For patients with high SLC25A17 expression, the OS and PFS were shorter than those with low SLC25A17 expression, indicating a worse prognosis. The expression of SLC25A17 varied in different clinical features. Univariate Cox and multivariate COX analyses showed that SLC25A17, age, and lymph node metastasis are independent prognostic risk factors for HNSCC, and the survival prediction model based on these factors had reliable predictive value. Patients in the low-expression group exhibited more immune cell infiltration, higher TME scores, higher IPS scores and lower TIDE scores than those in the high-expression groups, suggesting better immunotherapeutic response with lower SLC25A17 expression. Moreover, patients in the high-expression group were more sensitive to chemotherapy.
SLC25A17 can effectively predict the prognosis of HNSCC patients and could be a precise individual-targeted indicator for the treatment of HNSCC patients.
本研究旨在探讨 SLC25A17 在头颈部鳞状细胞癌（HNSCC）患者预后和肿瘤微环境（TME）中的预测价值，并为临床个体化治疗提供思路。
首先通过 TIMER 2.0 数据库对 SLC25A17 在不同肿瘤中的差异表达进行泛癌分析。随后，从 TCGA 数据库获取 HNSCC 患者的 SLC25A17 表达及相关临床信息，并根据 SLC25A17 表达的中位数将患者分为两组。采用 K‒M 生存分析比较两组患者的总生存期（OS）和无进展生存期（PFS）。采用 Wilcoxon 检验比较 SLC25A17 在不同临床特征中的分布，采用单因素 Cox 和多因素 Cox 分析筛选独立预后因素，建立预测列线图。绘制校准曲线验证预测 1 年、3 年和 5 年生存率的可靠性，并用另一个队列（GSE65858）进行外部验证。采用基因集富集分析比较富集通路，并使用 CIBERSORT 和 estimate 包评估免疫微环境。此外，还通过 TISCH 的单细胞 RNA-seq 分析 SLC25A17 在免疫细胞中的表达水平。比较两组患者的免疫治疗反应和化疗药物敏感性，以指导精准治疗。应用 TIDE 数据库预测 TCGA-HNSC 队列中免疫逃逸的可能性。
与正常样本相比，SLC25A17 在 HNSCC 肿瘤样本中的表达明显升高。高 SLC25A17 表达患者的 OS 和 PFS 短于低 SLC25A17 表达患者，提示预后较差。SLC25A17 的表达在不同临床特征中存在差异。单因素 Cox 和多因素 COX 分析表明，SLC25A17、年龄和淋巴结转移是 HNSCC 的独立预后危险因素，基于这些因素的生存预测模型具有可靠的预测价值。低表达组的免疫细胞浸润、TME 评分、IPS 评分更高，TIDE 评分更低，提示 SLC25A17 低表达时免疫治疗反应更好。此外，高表达组患者对化疗更敏感。
SLC25A17 可有效预测 HNSCC 患者的预后，可能成为 HNSCC 患者个体化治疗的精准指标。
