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FAM117A是肺腺癌的一种新的预后标志物,并预测对PD0332991的敏感性。

FAM117A Is a New Prognostic Marker of Lung Adenocarcinoma and Predicts Sensitivity to PD0332991.

作者信息

Wu Chao, Zhang Jiajin, Wang Kuan, Fan Mengjiao, Hu Yi

机构信息

Department of Oncology, Chinese PLA General Hospital, Beijing 100853, China.

Department of Systems Surgery, Chinese PLA General Hospital, Beijing 100853, China.

出版信息

Evid Based Complement Alternat Med. 2022 Mar 3;2022:3945446. doi: 10.1155/2022/3945446. eCollection 2022.

Abstract

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.

摘要

肺癌是全球第二常见的癌症,也是癌症死亡的主要原因。细胞周期加速进展是癌症的一个特征明确的标志。本研究旨在确定肺癌患者临床预后的生物标志物及其对细胞周期蛋白依赖性激酶(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,以确定与生存相关的基因;然后使用细胞增殖试验、集落形成试验、流式细胞术、蛋白质印迹、5-乙炔基-2'-脱氧尿苷(EDU)标记和异种移植模型来证实所鉴定因素的潜在作用。我们的结果确定FAM117A表达降低是与不良预后最相关的生存因素。FAM117A过表达时,细胞周期从G1期到S期的转变受到抑制,而FAM117A敲低时则得到促进。因此,FAM117A缺失诱导的肿瘤细胞生长被已获批用于癌症治疗的PD0332991完全阻断。总之,我们的研究确定FAM117A是肺癌患者不良预后的一个新的预后标志物,可预测对PD0332991治疗的敏感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edab/8913056/a181f131de27/ECAM2022-3945446.001.jpg

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