Liu Jiamin, Zhang Qiang, He Ling, Hu Huangyu, Wang Yixuan, Xie Ping
Department of Gynecology, Sichuan Provincial Hospital of Traditional Chinese Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People's Republic of China.
Onco Targets Ther. 2025 Jan 22;18:107-127. doi: 10.2147/OTT.S491310. eCollection 2025.
Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated membrane fusion is crucial for autophagy, making YKT6, a key modulator of cell membrane fusion, a potential target for cancer therapy. However, its oncogenic role across different cancers remains unclear. This study was to investigate the prognostic value and potential immunological functions of YKT6, including cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC).
Multiple bioinformatics databases, including The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx) databases, were used to investigate the correlation of the YKT6 expression pattern with the pathological stage and survival rate across cancers. Furthermore, ImmuCellAI, the UCSC Xena platform, and the ESTIMATE algorithm were subsequently utilized to explore the potential relationship between YKT6 expression, the tumor microenvironment, and tumor immune infiltration. Profiling of YKT6 gene mutation and amplification, methylation, and copy number alteration (CNA) was performed on the basis of the TCGA database. Moreover, q-PCR, TMA staining, and siRNA assays were used to validate the cancer-promoting role of YKT6 in CESCs.
Our results reveal that YKT6 is a potential prognostic and cancer immunity biomarker. Elevated YKT6 expression is correlated with poor overall survival (OS) and disease-free survival (DFS). Distinct gene mutation, methylation, and CNA patterns for YKT6 were found in certain types of cancers. The correlation of YKT6 expression with tumor-infiltrating immune cells was verified by analyzing the StromalScore, ESTIMATEScore, ImmuneScore, and tumor purity. In vitro analysis confirmed that YKT6 was highly expressed in advanced-grade CESCs and that the knockdown of YKT6 inhibited the proliferation of cervical cancer cells.
The SNARE protein YKT6 serves as a biomarker and candidate oncogene with actionable mutations. Moreover, YKT6 has the potential to be a prognostic indicator in CESCs. Targeting YKT6 could enhance autophagy regulation and improve therapeutic strategies for personalized cancer treatment.
可溶性N - 乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）介导的膜融合对自噬至关重要，使得YKT6（细胞膜融合的关键调节因子）成为癌症治疗的潜在靶点。然而，其在不同癌症中的致癌作用仍不清楚。本研究旨在探讨YKT6在宫颈鳞状细胞癌和宫颈管腺癌（CESC）中的预后价值和潜在免疫功能。
使用多个生物信息学数据库，包括癌症基因组图谱（TCGA）、癌细胞系百科全书（CCLE）和基因型 - 组织表达（GTEx）数据库，研究YKT6表达模式与不同癌症的病理分期和生存率之间的相关性。此外，随后利用ImmuCellAI、加州大学圣克鲁兹分校Xena平台和ESTIMATE算法来探索YKT6表达、肿瘤微环境和肿瘤免疫浸润之间的潜在关系。基于TCGA数据库对YKT6基因的突变、扩增、甲基化和拷贝数改变（CNA）进行分析。此外，采用q - PCR、组织微阵列染色和小干扰RNA（siRNA）实验来验证YKT6在CESC中的促癌作用。
我们的结果表明YKT6是一种潜在的预后和癌症免疫生物标志物。YKT6表达升高与总生存期（OS）和无病生存期（DFS）较差相关。在某些类型的癌症中发现了YKT6不同的基因突变、甲基化和CNA模式。通过分析基质评分、ESTIMATE评分、免疫评分和肿瘤纯度，验证了YKT6表达与肿瘤浸润免疫细胞的相关性。体外分析证实YKT6在高级别CESC中高表达，并且敲低YKT6可抑制宫颈癌细胞的增殖。
SNARE蛋白YKT6作为具有可操作突变的生物标志物和候选癌基因。此外，YKT6有可能成为CESC中的预后指标。靶向YKT6可增强自噬调节并改善个性化癌症治疗的策略。
