Clin Lab. 2020 Dec 1;66(12). doi: 10.7754/Clin.Lab.2020.200302.
Systematic screening for serum-derived biomarkers of cisplatin (DDP) resistance in gastric cancer (GC) remains unreported. The current study aimed to investigate differentially expressed serum miRNAs in GC patients with DDP sensitivity and resistance and their ability to predict cisplatin treatment effectiveness.
The DDP-resistant GC cell line MGC803/DDP was established for screening these dysregulated miRNAs through small RNA sequencing (sRNA-seq), and the miRNA functions were annotated by bioinformatics analysis. RT-qPCR validated the relative miRNA transcription levels in GC cells and sera from 74 GC patients. The associations between the patient clinical parameters and miRNA expression were analyzed. The diagnostic value was evaluated using receiver operating characteristic (ROC) analysis.
sRNA-seq identified 35 miRNAs with differential expression between MGC803/DDP cells and MGC803 cells, with miR-3180-3p as the most significantly upregulated miRNA and miR-124-3p as the most significantly downregulated miRNA in MGC803/DDP cells. Clinical data analysis showed that compared with their expression in chemosensitive patients, miR-3180-3p expression was significantly upregulated and miR-124-3p expression was downregulated in chemoresistant GC patients (both p < 0.0001). A combination of the two miRNAs effectively dis-tinguished the chemoresistant GC patients from the chemosensitive GC patients (AUC = 0.946 ± 0.023, 95% CI = 0.900 - 0.991, p < 0.001, SE = 85.0%, SP = 82.4%). Downregulated miR-124-3p and upregulated miR-3180-3p were significantly correlated with a high TNM stage.
The differentially expressed circulatory markers miR-124-3p, miR-3180-3p, and their combination can serve as serum-based biomarkers to predict the therapeutic benefit of DDP in GC.
胃癌（GC）患者血清中顺铂（DDP）耐药的系统筛查标志物仍未见报道。本研究旨在探讨 DDP 敏感和耐药 GC 患者血清中差异表达的 miRNA 及其预测顺铂治疗效果的能力。
通过小 RNA 测序（sRNA-seq）筛选 DDP 耐药 GC 细胞系 MGC803/DDP 中这些失调的 miRNA，通过生物信息学分析注释 miRNA 功能。RT-qPCR 验证了 74 例 GC 患者的 GC 细胞和血清中相对 miRNA 转录水平。分析了患者临床参数与 miRNA 表达的相关性。采用受试者工作特征（ROC）分析评估诊断价值。
sRNA-seq 鉴定出 MGC803/DDP 细胞与 MGC803 细胞之间差异表达的 35 个 miRNA，其中 miR-3180-3p 在 MGC803/DDP 细胞中表达上调最显著，miR-124-3p 表达下调最显著。临床数据分析显示，与化疗敏感患者相比，化疗耐药 GC 患者 miR-3180-3p 表达显著上调，miR-124-3p 表达下调（均 p<0.0001）。两种 miRNA 的组合能有效区分化疗耐药和化疗敏感的 GC 患者（AUC=0.946±0.023，95%CI=0.900-0.991，p<0.001，SE=85.0%，SP=82.4%）。下调的 miR-124-3p 和上调的 miR-3180-3p 与较高的 TNM 分期显著相关。
差异表达的循环标志物 miR-124-3p、miR-3180-3p 及其组合可作为血清标志物预测 GC 患者 DDP 的治疗效果。
