Ghoorun Roshan Ara, Wu Xiao-Hua, Chen Hong-Lei, Ren Dong-Lin, Wu Xiao-Bin
Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
Department of Oncology, Longhu People's Hospital, Shantou, Guangdong, People's Republic of China.
Onco Targets Ther. 2019 Dec 30;12:11567-11577. doi: 10.2147/OTT.S221943. eCollection 2019.
Although our understanding on gastric cancer biology is better than a decade ago, its practical effect on screening and diagnosis remains limited. Moreover, there are no markers that can be accurately used in the clinic to diagnose early-stage gastric cancer or monitor the patient's response to therapy. Herein, we investigate whether FKBP14 is involved in the progression of gastric cancer.
The AGS cell line was chosen for over-expression analysis, whereas the SGC-7901 cell line was selected for knock-down analysis. AGS cells were transfected with an FKBP14 overexpression plasmid (AGS-PLV.O-FLAG). The expression pattern of FKBP14 in both cell lines was determined by Western blot and RT-PCR. Cell proliferation was assessed using Cell Counting Kit-8, whereas apoptosis was performed using flow cytometry. The expression of FKBP14 in 70 Chinese patients with gastric cancer was also investigated using tissue microarrays and compared with gastric cancer patients from The Cancer Genome Atlas.
FKBP14 was highly expressed in SGC7901 and had a relatively low expression in AGS cells. Upregulation of FKBP14 in AGS cells promoted migration and invasion and inhibits apoptosis. Knock-down of FKBP14 resulted in a suppression in migration and invasion and promoted apoptosis in the SGC-7901 cell line. Effectively, gastric cancer patients had a higher expression of FKBP14, with a lower survival rate ( = 0.028). Patients with a high expression of FKBP14 were significantly correlated with lymph node metastasis ( =0.016), and an advanced histologic grade ( =0.021).
FKBP14 is often up-regulated in gastric cancer. Patients with a high expression of FKBP14 are usually associated with worse overall survival. FKBP14 is an oncogene in gastric cancer, and is a potential biomarker for GC diagnosis, invasion, and prognosis.
尽管我们对胃癌生物学的理解比十年前有所进步，但其在筛查和诊断方面的实际效果仍然有限。此外，目前尚无能够在临床上准确用于诊断早期胃癌或监测患者对治疗反应的标志物。在此，我们研究FKBP14是否参与胃癌的进展。
选择AGS细胞系进行过表达分析，而选择SGC-7901细胞系进行敲低分析。用FKBP14过表达质粒（AGS-PLV.O-FLAG）转染AGS细胞。通过蛋白质免疫印迹法和逆转录-聚合酶链反应确定两种细胞系中FKBP14的表达模式。使用细胞计数试剂盒-8评估细胞增殖，而通过流式细胞术检测细胞凋亡。还使用组织芯片研究了70例中国胃癌患者中FKBP14的表达，并与来自癌症基因组图谱的胃癌患者进行比较。
FKBP14在SGC7901中高表达，在AGS细胞中表达相对较低。AGS细胞中FKBP14的上调促进了迁移和侵袭并抑制了细胞凋亡。敲低FKBP14导致SGC-7901细胞系的迁移和侵袭受到抑制，并促进了细胞凋亡。实际上，胃癌患者FKBP14表达较高，生存率较低（P = 0.028）。FKBP14高表达的患者与淋巴结转移（P = 0.016）和高级别组织学分级（P = 0.021）显著相关。
FKBP14在胃癌中常上调。FKBP14高表达的患者通常总生存期较差。FKBP14是胃癌中的一种癌基因，是胃癌诊断、侵袭和预后的潜在生物标志物。
