Huang Guocheng, Li Xinji, Chen Zebo, Wang Jingyao, Zhang Chunduo, Chen Xuan, Peng Xiqi, Liu Kaihao, Zhao Liwen, Lai Yongqing, Ni Liangchao
Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Guangdong, 518036, Shenzhen, People's Republic of China.
Shantou University Medical College, Shantou, Guangdong, 515041, China.
Pathol Oncol Res. 2020 Oct;26(4):2425-2434. doi: 10.1007/s12253-020-00842-y. Epub 2020 Jun 18.
Renal cell carcinoma (RCC) accounts for about 120,000 death each year. Although surgery is a routine treatment, RCC could be fatal if not diagnosed at an early stage. This study aims to search for suitable serum biomarkers and construct a miRNA panel with high diagnostic sensitivity or specificity.
Totally 146 RCC patients and 150 normal control were involved in this three-stage study. Serum expression levels of 30 miRNAs selected from literature were tested by reverse transcription quantitative PCR (RT-qPCR) in the screening stage, the testing stage, and the validation stage. The diagnostic efficiency of miRNAs was evaluated by receiver operating characteristic (ROC) curve and area under curve (AUC) analysis. A panel with the highest diagnostic efficiency was constructed by backward stepwise logistic regression analysis. Additionally, bioinformatics analysis was used to investigate potential biological functions and mechanisms of candidate miRNAs.
MiR-224-5p, miR-34b-3p, miR-129-2-3p and miR-182-5p with low to moderate diagnostic ability (AUC = 0.692, 0.778, 0.687 and 0.745, respectively) were selected as candidate miRNAs after the three-stage study. The final diagnostic panel was consisted by miR-224-5p, miR-34b-3p and miR-182-5p with AUC = 0.855. No significance has been found between these four miRNAs and tumor location, Fuhrman Grade and AJCC clinical stages of RCC. Bioinformatic analysis suggested that the three-miRNAs panel may participate in tumorigenesis of RCC by targeting CORO1C.
The three-miRNA panel in serum could serve as a non-invasive diagnostic biomarker of RCC.
肾细胞癌（RCC）每年导致约12万人死亡。尽管手术是常规治疗方法，但如果未早期诊断，RCC可能会致命。本研究旨在寻找合适的血清生物标志物，并构建具有高诊断敏感性或特异性的miRNA组合。
本三阶段研究纳入了146例RCC患者和150例正常对照。在筛选阶段、测试阶段和验证阶段，通过逆转录定量PCR（RT-qPCR）检测从文献中选取的30种miRNA的血清表达水平。通过受试者工作特征（ROC）曲线和曲线下面积（AUC）分析评估miRNA的诊断效率。通过向后逐步逻辑回归分析构建诊断效率最高的组合。此外，使用生物信息学分析来研究候选miRNA的潜在生物学功能和机制。
经过三阶段研究，miR-224-5p、miR-34b-3p、miR-129-2-3p和miR-182-5p被选为候选miRNA，其诊断能力为低到中等（AUC分别为0.692、0.778、0.687和0.745）。最终诊断组合由miR-224-5p、miR-34b-3p和miR-182-5p组成，AUC为0.855。这四种miRNA与RCC的肿瘤位置、Fuhrman分级和AJCC临床分期之间未发现显著差异。生物信息学分析表明，这三种miRNA组合可能通过靶向CORO1C参与RCC的肿瘤发生。
血清中的三种miRNA组合可作为RCC的非侵入性诊断生物标志物。
