Department of Otorhinolaryngology-Head & Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Biomolecules. 2022 Jul 27;12(8):1034. doi: 10.3390/biom12081034.
Background: Genomic instability is implicated in the initiation and progression of oral squamous cell carcinoma (OSCC). Tumor suppressor Secreted Frizzled-Related Protein 1 (SFRP1) may participate in the aberrant evolution of OSCC, the intrinsic molecular mechanisms of which may provide effective therapeutic targets. Methods: A bioinformatics analysis was carried out on a publicly available database using R language to map the prognostic value, immune infiltration and enrichment of SFRP1 expression. Subsequently, in vitro experiments were conducted to unveil the biological function of SFRP1. Results: SFRP1 was found to be ubiquitously lowly expressed in OSCC using a Wilcoxon rank-sum test. Univariate analysis confirmed that those patients characterized by a low SFRP1 expression were significantly associated with advanced T-stage, clinical stage and poor mortality (p < 0.05). Furthermore, SFRP1 displayed a positive performance in tumor immune infiltration, especially in mast cells. Functional annotations indicated that highly expressed SFRP1 was associated with membrane potential and passive transmembrane transporter activity and it was mainly enriched in calcium pathway and neuroactive ligand−receptor interaction. In vitro, the overexpression of SFRP1 inhibited its proliferation, migration, and invasion and resulted in G0+G1 phase arrest within Cal27 cells (p < 0.05). Conclusions: The bioinformation data suggest that SFRP1 expression provides an insight into the risk and prognostic stratification in OSCC. SFRP1 was validated as a potential biomarker with anticarcinogenic behaviors for use in targeted therapy.
基因组不稳定性与口腔鳞状细胞癌(OSCC)的发生和发展有关。肿瘤抑制因子分泌型卷曲相关蛋白 1(SFRP1)可能参与 OSCC 的异常进化,其内在的分子机制可能为提供有效的治疗靶点。方法:使用 R 语言对公开数据库进行生物信息学分析,以绘制 SFRP1 表达的预后价值、免疫浸润和富集图谱。随后,进行了体外实验以揭示 SFRP1 的生物学功能。结果:通过 Wilcoxon 秩和检验发现 SFRP1 在 OSCC 中普遍低表达。单因素分析证实,SFRP1 低表达的患者与晚期 T 分期、临床分期和较差的死亡率显著相关(p < 0.05)。此外,SFRP1 在肿瘤免疫浸润中表现出阳性表现,尤其是肥大细胞。功能注释表明,高表达的 SFRP1 与膜电位和被动跨膜转运体活性相关,主要富集在钙途径和神经活性配体-受体相互作用中。在体外,SFRP1 的过表达抑制了 Cal27 细胞的增殖、迁移和侵袭,并导致 G0+G1 期停滞(p < 0.05)。结论:生物信息学数据表明,SFRP1 的表达提供了对 OSCC 风险和预后分层的深入了解。SFRP1 被验证为一种具有抗癌行为的潜在生物标志物,可用于靶向治疗。