PTEN 作为头颈部鳞状细胞癌的新型诊断和预后生物标志物

Zain Ali, Akbar Ali
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摘要

这篇综述文章通过全面的表达和甲基化检查、基因突变调查和预后评估,探讨了磷酸酶和天丝同源物(PTEN)在头颈部鳞状细胞癌(HNSCC)中的作用。利用 UALCAN 信息库,PTEN 表达检查发现了从正常对照样本中分离出来的 HNSCC 细胞中的关键过表达,从而提出了它在 HNSCC 增殖中的作用。此外,对不同临床限制条件下的 PTEN 表达进行的分析表明,在 HNSCC 患者的不同癌症发展阶段、种族群体、性别和年龄段中,PTEN 的表达都出现了严重的上调,这表明它在癌症复制中起着重要作用。利用 GEPIA2.0 在线工具对 PTEN 的表达进行了验证,结果表明 PTEN 的表达在 HNSCC 癌症改善过程中表现得尤为明显,与正常对照样本不同。因此,在癌症发展的不同阶段对PTEN进行验证,结果显示在四个阶段中的每一个阶段都存在表达失调,其中I期的表达量最高,而IV期的表达量最低。因此,本研究对 PTEN 启动子甲基化水平进行了调查,找出了 HNSCC 样本与正常对照样本之间的基本关系。分析不同临床界限的启动子甲基化发现了巨大的差异,在恶性生长阶段、种族组、性别和年龄组中都能看到特定的甲基化模式。利用KM plotter工具进行的总生存期和无病生存期(OS和DFS)分析表明,HNSCC患者的PTEN表达水平与总生存期之间存在重要关系,PTEN高表达与PTEN低表达水平相比具有明显差异。此外,在无病生存期(DFS)评估中,PTEN 低表达的 HNSCC 患者的无病生存期比 PTEN 高表达的 HNSCC 患者要长。此外,为了验证PTEN表达与生存的关系,研究将HNSCC患者分为PTEN低表达组和高表达组。在HNSCC中,当PTEN低表达与PTEN高表达形成对比时,PTEN低表达与高总生存率(OS)相关。同样,研究发现,在HNSCC中,当PTEN低表达水平与PTEN高表达组形成鲜明对比时,PTEN低表达水平与高DFS相关。通过 cBioPortal 进行的基因突变分析发现,HNSCC 中 PTEN 突变的比例极低,主要是框架内突变、错义突变、剪接突变、截短突变和结构变异,这表明它们在 HNSCC 中 PTEN 失调中具有基础意义。进一步研究PTEN分子成分及其在HNSCC微环境中的交换,可能会为指定治疗和精确用药方法揭示新的道路,以对抗这种有害的疾病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
PTEN as a Novel Diagnostic and Prognostic Biomarker of Head and Neck Squamous Cell Carcinoma
This review article explores phosphatase and tensin homolog (PTEN)’s role in head and neck squamous cell carcinoma (HNSCC) through comprehensive expression and methylation examinations, genetic mutation investigation, and prognostic evaluation. Using the UALCAN informational collection, PTEN expression examination uncovered a critical over-expression in HNSCC cells isolated from normal control samples, proposing its role in HNSCC multiplication. Further, analysis of PTEN expression across various clinical limits has shown critical up-regulation in different cancer development stages, racial groups, gender, and age classes within the context of HNSCC patients, suggesting its major role in cancer duplication. PTEN expression was validated by utilizing the GEPIA2.0 online tool, which showed PTEN expression was particularly significantly expressed in HNSCC cancer improvement when it appeared differently from normal control samples. Accordingly, examining PTEN validation across different phases of cancer advancement showed dysregulation in each of the four phases with the most raised expression in stage I and the least expression in stage IV. Thus, this study investigated the promoter methylation level of PTEN, figuring out a basic relationship between HNSCC samples and normal control samples. Analyzing promoter methylation across various clinical limits uncovered massive variations, with specific methylation patterns seen across malignant growth stages, race groups, gender, and age groups. Overall survival and disease-free survival (OS and DFS) utilizing the KM plotter tool showed a critical relationship between PTEN expression levels in HNSCC patients, showing high PTEN expression exhibited good overall survival when showed up distinctively comparable to low PTEN expression levels. In addition, in disease-free survival (DFS) evaluation HNSCC patients showing low PTEN expression experienced great DFS relative to HNSCC patients with high PTEN expression. Moreover, to validate PTEN expression against survival, the study examined the HNSCC patients into low and high-expression groups of PTEN. In HNSCC, low PTEN expression was connected with great overall survival (OS) when it appeared contrastingly relative to the high PTEN expression. In like manner, the study found that low PTEN expression level was connected with great DFS in HNSCC when it appeared contrastingly related to the high PTEN expression group. Genetic mutation analysis via cBioPortal identifies a minimal proportion of PTEN mutations in HNSCC, predominantly in-frame mutation, missense mutation, splice mutation, truncating mutation, and structural variant, indicating their basal significance in PTEN dysregulation within HNSCC. Further investigation of PTEN molecular components and their exchange inside the HNSCC microenvironment might disclose novel roads for designated treatment and accurate medication approaches in battling this harmful disease.
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