FAM117A Is a New Prognostic Marker of Lung Adenocarcinoma and Predicts Sensitivity to PD0332991.
FAM117A Is a New Prognostic Marker of Lung Adenocarcinoma and Predicts Sensitivity to PD0332991.
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DOI：
10.1155/2022/3945446
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Hu Y
中科院分区：
文献类型：
--
作者：
Wu C;Zhang J;Wang K;Fan M;Hu Y
肺癌是第二大常见癌症，也是全球癌症死亡的主要原因。加速的细胞周期进程是癌症的一个充分表征的标志。本研究旨在确定肺癌患者临床结局的生物标志物及其对CDK抑制剂的敏感性。为此，首先对来自癌症基因组图谱（TCGA）的转录组数据集进行生物信息学分析以鉴定存活相关基因;然后使用细胞增殖测定、集落形成测定、流式细胞术、蛋白质印迹、EDU标记和异种移植模型来确认所鉴定因子的潜在作用。我们的研究结果表明，FAM 117 A表达下降是导致预后不良的最重要的生存相关因素。FAM 117 A过表达可抑制细胞周期从G1期向S期的转变，而FAM 117 A敲低可促进细胞周期从G1期向S期的转变。因此，FAM 117 A消耗诱导的肿瘤细胞生长被PD 0332991治疗完全阻断，PD 0332991已被批准用于癌症治疗。总之，我们的工作将FAM 117 A确定为肺癌患者预后不良的新预后标志物，预测对PD 0332991治疗的敏感性。
Lung cancer is the second most common cancer and the leading cause for cancer mortality worldwide. Accelerated cell cycle progression is a well-characterized hallmark for cancer. The present study aims to identify biomarkers for clinical outcomes of lung cancer patients and their sensitivity to CDK inhibitors. To this end, bioinformatics analysis of transcriptome datasets from the Cancer Genome Atlas (TCGA) was first performed to identify survival-related genes; cell proliferation assay, colony formation assay, flow cell cytometry, western blot, EDU labelling, and xenograft models were then used to confirm the potential roles of the identified factors. Our results identified the decreased FAM117A expression as the most significant survival related factor for poor outcome. The cell cycle transition from G1 to S phase was suppressed upon FAM117A overexpression and was promoted upon FAM117A knockdown. Accordingly, the tumor cell growth induced by FAM117A depletion was completely blocked by treatment with PD0332991, which has been approved for cancer therapy. In summary, our work identified FAM117A as a new prognostic marker for poor outcomes of lung cancer patients, predicting sensitivity to PD0332991 treatment.
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