{"title":"Pan-Cancer Analysis Identifies YKT6 as a Prognostic and Immunotherapy Biomarker, with an Emphasis on Cervical Cancer.","authors":"Jiamin Liu, Qiang Zhang, Ling He, Huangyu Hu, Yixuan Wang, Ping Xie","doi":"10.2147/OTT.S491310","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":19534,"journal":{"name":"OncoTargets and therapy","volume":"18 ","pages":"107-127"},"PeriodicalIF":2.7000,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11766309/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"OncoTargets and therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/OTT.S491310","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
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.
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.
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