Lymphatic metastasis(LM)emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma(HSPSCC),chiefly contributing to treatment inefficacy.This study aimed to scrutinize the prognostic relevan...Lymphatic metastasis(LM)emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma(HSPSCC),chiefly contributing to treatment inefficacy.This study aimed to scrutinize the prognostic relevance of HSP90AA1 and its potential regulatory mechanism of concerning LM in HPSCC.Methods:In a preceding investigation,HSP90AA1,a differential gene,was discovered through transcriptome sequencing of HPSCC tissues,considering both the presence and absence of LM.Validation of HSP90AA1 expression was accomplished via qRT-PCR,western-blotting(WB),and immunohistochemistry(IHC),while its prognostic significance was assessed employing Kaplan–Meier survival analysis(KMSA),log-rank test(LR),and Cox’s regression analysis(CRA).Bioinformatics techniques facilitated the prediction and analysis of its plausible mechanisms in LM,further substantiated by in vitro and in vivo experiments utilizing FaDu cell lines.Results:HSP90AA1 is substantially upregulated in HPSCC with LM and is identified as an independent prognostic risk determinant.The down-regulation of HSP90AA1 can achieve inhibition of tumor cell proliferation,migration and invasion.Both in vivo experiments and Bioinformatics exploration hint at promoting LM by Epithelial-mesenchymal transition(EMT),regulated by HSP90AA1.Conclusions:HSP90AA1,by controlling EMT,can foster LM in HPSCC.This finding sets the foundation for delving into new therapeutic targets for HPSCC.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82173303)Natural Science Foundation of Chongqing,China(Grant No.cstc2021ycjh-bgzxm0149).
文摘Lymphatic metastasis(LM)emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma(HSPSCC),chiefly contributing to treatment inefficacy.This study aimed to scrutinize the prognostic relevance of HSP90AA1 and its potential regulatory mechanism of concerning LM in HPSCC.Methods:In a preceding investigation,HSP90AA1,a differential gene,was discovered through transcriptome sequencing of HPSCC tissues,considering both the presence and absence of LM.Validation of HSP90AA1 expression was accomplished via qRT-PCR,western-blotting(WB),and immunohistochemistry(IHC),while its prognostic significance was assessed employing Kaplan–Meier survival analysis(KMSA),log-rank test(LR),and Cox’s regression analysis(CRA).Bioinformatics techniques facilitated the prediction and analysis of its plausible mechanisms in LM,further substantiated by in vitro and in vivo experiments utilizing FaDu cell lines.Results:HSP90AA1 is substantially upregulated in HPSCC with LM and is identified as an independent prognostic risk determinant.The down-regulation of HSP90AA1 can achieve inhibition of tumor cell proliferation,migration and invasion.Both in vivo experiments and Bioinformatics exploration hint at promoting LM by Epithelial-mesenchymal transition(EMT),regulated by HSP90AA1.Conclusions:HSP90AA1,by controlling EMT,can foster LM in HPSCC.This finding sets the foundation for delving into new therapeutic targets for HPSCC.