Division of Hematology and Oncology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
J Cell Mol Med. 2022 Nov;26(21):5452-5462. doi: 10.1111/jcmm.17569. Epub 2022 Oct 13.
Tumour necrosis family superfamily (TNFSF) member 15 (TNFSF15), encoded by TNFSF15, regulates immune responses and inflammation. However, the roles of TNFSF15 single-nucleotide variants (SNVs; formerly SNPs) in oral cavity squamous cell carcinoma (OCSCC) remain unclear. This case-control study included 2523 participants (1324 patients with OCSCC [52.5%] and 1199 healthy controls [47.5%]). The effects of TNFSF15 rs3810936, rs6478108 and rs6478109 on cancer development and prognosis were analysed by real-time PCR genotype assay. The Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases were used to validate our findings. The results demonstrated that the patients with altered TNFSF15 SNVs had poorer histological differentiation than did those with wild-type alleles. TNFSF15 SNVs were significantly associated with moderate-to-poor histological differentiation in univariate logistic regression. In the GTEx database, the expression of altered TNFSF15 SNVs in whole blood was lower than that of wild-type alleles. However, the expression of altered SNVs in the upper aerodigestive mucosa was higher than that of wild-type alleles. In the TCGA database, the patients with higher TNFSF15 expression had shorter overall survival than did those with lower TNFSF15 expression, especially for human papillomavirus-negative and advanced staging groups. In conclusion, although TNFSF15 SNVs did not affect OCSCC development, the patients with altered TNFSF15 SNVs exhibited poorer histological differentiation. The patients with higher TNFSF15 expression had poorer prognosis than did those with lower TNFSF15 expression.
肿瘤坏死因子超家族成员 15（TNFSF15），由 TNFSF15 编码，调节免疫反应和炎症。然而，TNFSF15 单核苷酸变异（SNV；以前称为 SNPs）在口腔鳞状细胞癌（OCSCC）中的作用尚不清楚。这项病例对照研究纳入了 2523 名参与者（1324 名 OCSCC 患者[52.5%]和 1199 名健康对照者[47.5%]）。通过实时 PCR 基因型检测分析了 TNFSF15 rs3810936、rs6478108 和 rs6478109 对癌症发展和预后的影响。使用基因型组织表达（GTEx）和癌症基因组图谱（TCGA）数据库验证了我们的研究结果。结果表明，与野生型等位基因相比，改变的 TNFSF15 SNV 患者的组织学分化较差。在单变量逻辑回归中，TNFSF15 SNVs 与中至差的组织学分化显著相关。在 GTEx 数据库中，改变的 TNFSF15 SNVs 在全血中的表达低于野生型等位基因。然而，改变的 SNVs 在上呼吸道黏膜中的表达高于野生型等位基因。在 TCGA 数据库中，TNFSF15 表达较高的患者总生存期短于 TNFSF15 表达较低的患者，尤其是在人乳头瘤病毒阴性和晚期分期组中。总之，尽管 TNFSF15 SNVs 不影响 OCSCC 的发展，但改变的 TNFSF15 SNVs 患者的组织学分化较差。TNFSF15 表达较高的患者预后较 TNFSF15 表达较低的患者差。
