Binang Helen Barong, Wang Yun-Shan, Tewara Marlvin Anemey, Du Lutao, Shi Shuang, Li Ning, Nsenga Ariston Gabriel Abakundana, Wang Chuanxin
Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
Department of Clinical Laboratory Diagnostics, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.
Oncol Lett. 2020 Mar;19(3):2431-2445. doi: 10.3892/ol.2020.11311. Epub 2020 Jan 16.
Gastric cancer (GC) is a type of cancer that is commonly diagnosed worldwide due to a lack of early diagnostic, prognostic and therapeutic targets for this disease. The aim of the present study was to examine the expression levels of five long non-coding RNAs, namely PTPRG antisense RNA 1 (PTPRG-AS1), forkhead box P4 antisense RNA 1 (FOXP4-AS1), bladder cancer-associated transcript 2 (BLACAT2), ZXF2 and upregulated in colorectal cancer (UCC), to study their associations with patient characteristics and assess their prognostic efficacy, in order to determine the possibility of their application as GC biomarkers. The expression levels of long non-coding RNAs (lncRNAs) were determined by reverse transcription-quantitative PCR analysis of 61 pairs of GC tissues and adjacent healthy gastric mucosa tissues and GC cell lines. The Chi-square test was conducted to assess the associations of lncRNA expression levels with clinical characteristics of patients. The effect of UCC on GC cell proliferation was determined using functional experiments. The prognostic efficacy of FOXP4-AS1, BLACAT2 and UCC were examined in the Gene Expression Profiling Interactive Analysis database and those of PTPRG-AS1 were examined in the Kaplan Meier Plot database. Gene alteration frequencies of PTPRG-AS1 and BLACAT2 in GC were identified using the cBioPortal for Cancer Genomics. PTPRG-AS1, FOXP4-AS1, BLACAT2, ZXF2 and UCC were found to be upregulated in GC cell lines and GC tissues compared with adjacent normal tissues. PTPRG-AS1 and ZXF2 expression levels were associated with the expression status of the cell proliferation marker Ki67. UCC promoted the proliferation of GC cells and was associated with lymph node metastasis. Increased expression of FOXP4-AS1 indicated a favorable outcome in terms of disease-free survival, whereas high expression of PTPRG-AS1 was associated with poor survival rates for patients in different GC risk groups. BLACAT2 gene mutation was associated with poor disease-free survival outcome for patients with GC. The results suggest that PTPRG-AS1, FOXP4-AS1, BLACAT2, ZXF2 and UCC are potential biomarkers for the detection of GC at the molecular level and may be used as potential targets for GC therapy. The individual roles of these lncRNAs may be utilized for prognostic predictions.
胃癌(GC)是一种在全球范围内普遍被诊断出的癌症,原因在于该疾病缺乏早期诊断、预后和治疗靶点。本研究的目的是检测五种长链非编码RNA的表达水平,即蛋白酪氨酸磷酸酶受体型G反义RNA 1(PTPRG-AS1)、叉头框P4反义RNA 1(FOXP4-AS1)、膀胱癌相关转录本2(BLACAT2)、ZXF2和在结直肠癌中上调的基因(UCC),研究它们与患者特征的关联并评估其预后效能,以确定它们作为胃癌生物标志物应用的可能性。通过对61对胃癌组织、相邻健康胃黏膜组织及胃癌细胞系进行逆转录定量PCR分析来测定长链非编码RNA(lncRNA)的表达水平。采用卡方检验评估lncRNA表达水平与患者临床特征的关联。利用功能实验确定UCC对胃癌细胞增殖的影响。在基因表达谱交互式分析数据库中检测FOXP4-AS1、BLACAT2和UCC的预后效能,在Kaplan Meier Plot数据库中检测PTPRG-AS1的预后效能。使用癌症基因组学cBioPortal识别胃癌中PTPRG-AS1和BLACAT2的基因改变频率。结果发现,与相邻正常组织相比,PTPRG-AS1、FOXP4-AS1、BLACAT2、ZXF2和UCC在胃癌细胞系和胃癌组织中上调。PTPRG-AS1和ZXF2的表达水平与细胞增殖标志物Ki67的表达状态相关。UCC促进胃癌细胞增殖并与淋巴结转移相关。FOXP4-AS1表达增加表明在无病生存方面有良好预后,而PTPRG-AS1高表达与不同胃癌风险组患者的低生存率相关。BLACAT2基因突变与胃癌患者的无病生存不良结局相关。结果表明,PTPRG-AS1、FOXP4-AS1、BLACAT2、ZXF2和UCC是在分子水平检测胃癌的潜在生物标志物,可能用作胃癌治疗的潜在靶点。这些lncRNA的个体作用可用于预后预测。