Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Int J Oncol. 2019 Sep;55(3):697-707. doi: 10.3892/ijo.2019.4838. Epub 2019 Jul 15.
Liver kinase b1 (LKB1) is a tumor suppressor, and the inactivated mutation frequency of LKB1 in lung adenocarcinoma is ~20%. The present study aimed to explore potential novel biomarkers in LKB1 mutant lung adenocarcinoma. Gene expression data from lung adenocarcinoma patients were downloaded from The Cancer Genome Atlas and the Gene Expression Omnibus databases. R software was used to analyze the gene expression profiles. Reverse transcription‑quantitative PCR (RT‑qPCR), western blot and immunohistochemistry (IHC) analyses were used to examine gene expression and function. Gene function was further explored via gene set enrichment analysis. A colony formation assay was used to evaluate cell proliferation. A wound‑healing assay and immunofluorescence analysis were used to evaluate cell migration and epithelial‑mesenchymal transition (EMT), respectively. Wound healing assay, immunofluorescence, western blot, RT‑qPCR and IHC results for EMT‑associated markers demonstrated that a loss of fibrinogen‑like 1 (FGL1) induced EMT in LKB1 mutant lung adenocarcinoma. RT‑qPCR and IHC analyses of angiogenesis‑related markers revealed that loss of FGL1 promoted angiogenesis in LKB1 mutant lung adenocarcinoma. Overall, the present results demonstrated that loss of FGL1 induced EMT and angiogenesis in LKB1 mutant lung adenocarcinoma. FGL1 may be a novel biomarker to indicate EMT and angiogenesis in patients with LKB1 mutant lung adenocarcinoma.
肝激酶 B1（LKB1）是一种肿瘤抑制因子，肺腺癌中 LKB1 的失活突变频率约为 20%。本研究旨在探索 LKB1 突变型肺腺癌中的潜在新型生物标志物。从癌症基因组图谱和基因表达综合数据库中下载肺腺癌患者的基因表达数据。使用 R 软件分析基因表达谱。通过逆转录-定量 PCR（RT-qPCR）、western blot 和免疫组织化学（IHC）分析来检测基因表达和功能。通过基因集富集分析进一步探索基因功能。通过集落形成实验评估细胞增殖。通过划痕愈合实验和免疫荧光分析分别评估细胞迁移和上皮-间充质转化（EMT）。EMT 相关标志物的划痕愈合实验、免疫荧光、western blot、RT-qPCR 和 IHC 结果表明，纤维蛋白原样 1（FGL1）的缺失在 LKB1 突变型肺腺癌中诱导 EMT。血管生成相关标志物的 RT-qPCR 和 IHC 分析显示，FGL1 的缺失促进了 LKB1 突变型肺腺癌中的血管生成。总体而言，本研究结果表明，FGL1 的缺失在 LKB1 突变型肺腺癌中诱导 EMT 和血管生成。FGL1 可能是 LKB1 突变型肺腺癌中 EMT 和血管生成的新型生物标志物。
