Pan-Cancer Analysis Identifies YKT6 as a Prognostic and Immunotherapy Biomarker, with an Emphasis on Cervical Cancer.

IF 2.7 4区医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

OncoTargets and therapy Pub Date : 2025-01-22 eCollection Date: 2025-01-01 DOI:10.2147/OTT.S491310

Jiamin Liu, Qiang Zhang, Ling He, Huangyu Hu, Yixuan Wang, Ping Xie

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引用次数: 0

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

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泛癌症分析确定YKT6作为预后和免疫治疗的生物标志物，重点是宫颈癌。

背景：可溶性n -乙基丙烯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，使细胞膜融合的关键调节剂YKT6成为癌症治疗的潜在靶点。然而，它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内膜腺癌（CESC）中的预后价值和潜在的免疫学功能。方法：利用美国癌症基因组图谱（TCGA）、癌症细胞系百科全书（CCLE）和基因型组织表达（GTEx）等多个生物信息学数据库，研究YKT6表达模式与肿瘤病理分期和生存率的相关性。随后，利用ImmuCellAI、UCSC Xena平台和ESTIMATE算法探索YKT6表达与肿瘤微环境和肿瘤免疫浸润之间的潜在关系。在TCGA数据库的基础上进行YKT6基因突变、扩增、甲基化和拷贝数改变（CNA）的分析。此外，采用q-PCR、TMA染色和siRNA检测来验证YKT6在CESCs中的促癌作用。结果：我们的研究结果表明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StromalScore、ESTIMATEScore、ImmuneScore和肿瘤纯度，验证YKT6表达与肿瘤浸润免疫细胞的相关性。体外分析证实，YKT6在晚期CESCs中高表达，敲低YKT6可抑制宫颈癌细胞的增殖。结论：SNARE蛋白YKT6是一种生物标志物和候选癌基因，具有可操作的突变。此外，YKT6有可能成为CESCs的预后指标。以YKT6为靶点可增强自噬调节，改善个体化癌症治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

OncoTargets and therapy BIOTECHNOLOGY & APPLIED MICROBIOLOGY-ONCOLOGY

CiteScore

9.70

自引率

0.00%

发文量

221

审稿时长

1 months

期刊介绍： OncoTargets and Therapy is an international, peer-reviewed journal focusing on molecular aspects of cancer research, that is, the molecular diagnosis of and targeted molecular or precision therapy for all types of cancer. The journal is characterized by the rapid reporting of high-quality original research, basic science, reviews and evaluations, expert opinion and commentary that shed novel insight on a cancer or cancer subtype. Specific topics covered by the journal include: -Novel therapeutic targets and innovative agents -Novel therapeutic regimens for improved benefit and/or decreased side effects -Early stage clinical trials Further considerations when submitting to OncoTargets and Therapy: -Studies containing in vivo animal model data will be considered favorably. -Tissue microarray analyses will not be considered except in cases where they are supported by comprehensive biological studies involving multiple cell lines. -Biomarker association studies will be considered only when validated by comprehensive in vitro data and analysis of human tissue samples. -Studies utilizing publicly available data (e.g. GWAS/TCGA/GEO etc.) should add to the body of knowledge about a specific disease or relevant phenotype and must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Bioinformatics studies must be validated using the authors’ own data through replication in an independent sample set and functional follow-up. -Single nucleotide polymorphism (SNP) studies will not be considered.