Zhang Jingpu, Song Yang, Zhang Chunlei, Zhi Xiao, Fu Hualin, Ma Yue, Chen Yunsheng, Pan Fei, Wang Kan, Ni Jian, Jin Weilin, He Xianli, Su Haichuan, Cui Daxiang
1. Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication of the Ministry of Education, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, P. R. China.
2. Gastrointestinal Division, Tangdu Hospital, Fourth Military Medical University, 569 Xinsi Road, Xi'an, 710038, P. R. China.
Theranostics. 2015 Apr 5;5(7):733-45. doi: 10.7150/thno.10305. eCollection 2015.
Gastric cancer (GC) is the second most common cancer in China and the second leading cause of cancer-related death in the world. Identifying circulating biomarkers is helpful to improve theranostics of gastric cancer. Herein, we are for the first time to report miR-16-5p and miR-19b-3p were identified to be the novel potential plasma biomarkers to detect gastric cancer. Differentially expressed miRNAs were initially screened out by genome-wide miRNA profiling microarrays between 16 plasma samples of gastric cancer and 18 matched normal controls, and then were quantified and validated by quantitative reverse transcription-PCR method between 155 gastric cancer cases and 111 normal controls. Additionally, 30 plasma samples from precancerous lesions and 18 paired samples from gastric cancer patients with gastrectomy were further detected. Results showed that based on two normalization methods, miR-16-5p and miR-19b-3p in plasma were found to be capable of distinguishing normal population from GC cases with different TNM stages and differentiation grades, particularly including the early cancer cases (P<0.05). And the two miRNAs were down-regulated in GC cases (FC<0.5). Especially, the down-regulation degree was correlated with the progression of the GC cases from the early stage to the advanced stage (0.2< r s<0.3, P<0.01). And the same weak down-regulation of the two biomarkers as the early GC occurred initially in the precancerous diseases (P<0.05). The corresponding performance of the two miRNAs to detect GC in ROC analysis gradually performed better with the disease progression from the earlier stages or lower grades to the advanced stages (TNM Ⅳ stage: AUC=0.832 for miR-16-5p; TNM Ⅲ stage: AUC=0.822 for miR-19b-3p) or high grade (Poorly differentiated: AUC=0.801, 0.791 respectively for miR-16-5p and miR-19b-3p). Additionally, miR-19b-3p remained down-regulated in patient plasma within 9 days after gastrectomy. In conclusion, miR-19b-3p and miR-16-5p maybe prospective biomarkers to detect gastric cancer and indicate its progression, and thus may own great potential in applications such as early screening and progression evaluation of gastric cancer in the near future.
胃癌（GC）是中国第二大常见癌症，也是全球癌症相关死亡的第二大主要原因。识别循环生物标志物有助于改善胃癌的诊疗。在此，我们首次报告miR-16-5p和miR-19b-3p被鉴定为检测胃癌的新型潜在血浆生物标志物。通过全基因组miRNA谱微阵列，在16例胃癌血浆样本和18例匹配的正常对照之间初步筛选出差异表达的miRNA，然后通过定量逆转录PCR方法在155例胃癌病例和111例正常对照之间进行定量和验证。此外，还进一步检测了30例癌前病变的血浆样本和18例接受胃切除术的胃癌患者的配对样本。结果显示，基于两种标准化方法，血浆中的miR-16-5p和miR-19b-3p能够区分正常人群与不同TNM分期和分化程度的胃癌病例，特别是早期癌症病例（P<0.05）。并且这两种miRNA在胃癌病例中表达下调（FC<0.5）。特别是，下调程度与胃癌病例从早期到晚期的进展相关（0.2<rs<0.3，P<0.01）。并且这两种生物标志物与早期胃癌相同的微弱下调最初出现在癌前疾病中（P<0.05）。在ROC分析中，这两种miRNA检测胃癌的相应性能随着疾病从早期或低级别进展到晚期（TNMⅣ期：miR-16-5p的AUC=0.832；TNMⅢ期：miR-19b-3p的AUC=0.822）或高级别（低分化：miR-16-5p和miR-19b-3p的AUC分别为0.801、0.791）而逐渐表现更好。此外，胃切除术后9天内患者血浆中的miR-19b-3p仍下调。总之，miR-19b-3p和miR-16-5p可能是检测胃癌并指示其进展的前瞻性生物标志物，因此在不久的将来可能在胃癌的早期筛查和进展评估等应用中具有巨大潜力。
Zotero 插件
