circ-0030343作为新的肾透明细胞癌发生发展分子标志物及其与Fuhrman分级相关性研究

Clear cell renal cell carcinoma (ccRCC) is the most frequent malignant neoplasm of the renal parenchyma. It has the highest mortality rate among other cancers, which is mainly triggered by its metastasis. The Fuhrman grading system is an independent indicator for aggressiveness and prognosis of ccRCC, but a precise diagnosis of preoperative Fuhrman grade is always compromised by invasive biopsy approaches. Circular RNAs (circRNAs) is a new regulatory molecule in tumorigenesis and development, and can be used as a potential noninvasive biomarker for tumor diagnosis. Our previous studies showed that circ_0030343 was highly expressed in the serum of ccRCC patients and its expression correlated with Fuhrman grading; circ_0030343 is associated with invasion and metastasis of ccRCC; the bioinformatics predicted targeting miRNA of circ_0030343 could regulate EMT pathway directly. To explore the role of circ_0030343 in ccRCC, we intend to first confirm that circ_0030343 works as a novel and excellent plasma biomarker for the diagnosis of ccRCC, and analyzes its correlation with Fuhrman classification by expanding the number of clinical samples.We believe this project will fully elucidate that circ_0030343 is involved in the initiation and development of ccRCC, which will prove their clinical utility in the diagnosis of ccRCC, and further provide a potential target and research direction for ccRCC therapy in the future.

肾透明细胞癌是最常见的肾恶性肿瘤，其治疗难点在于肾癌复发转移。Fuhrman分级能反映肾癌恶性程度且是其独立预后因子，却不能在患者治疗选择上提供帮助，且无法早期监测肿瘤复发、转移。研究表明，circRNA是肿瘤发生发展中新兴的调节分子，可作为潜在的肿瘤诊断标志。我们前期研究初步表明：circ_0030343在肾癌患者血清中高表达，且与Fuhrman分级相关；它在细胞中的表达与肾癌的侵袭和转移相关。生物信息预测circ_0030343的靶向miRNA 可直接调控EMT。因此，本项目拟扩大临床样本量，确认circ_0030343做为肾癌的分子标志作用，并将其与Fuhrman分级做关联分析。综上，通过阐述circ_0030343与肾癌发生发展过程的相关性，为肾癌的诊断提供新方法，为发展肾癌新疗法提供新靶点和研究方向。

肾透明细胞癌是最常见的肾恶性肿瘤，其治疗难点在于肾癌复发转移。Fuhrman分级能反映肾癌恶性程度且是其独立预后因子，却不能在患者治疗选择上提供帮助，且无法早期监测肿瘤复发、转移。本研究利用circRNA芯片鉴定出一系列差异表达的circRNAs，并对这些差异最显著circRNA进行癌组织、癌旁组织、患者以及正常血清的临床大标本验证，最终鉴定出circDVL1和circMYH9是肾透明细胞癌发生高度相关的分子标记物。同时对患者临床数据进行相关性分析，circDVL1表达量与Fuhrman分级呈密切相关性。本研究对circDVL1在肾透明细胞癌的功能进行深入研究。细胞水平实验证明circDVL1的高表达可以抑制细胞增殖、使细胞周期停滞在G0/S期以及诱导细胞凋亡。另外，裸鼠实验证明circDVL1的高表达同样抑制肿瘤体积和重量；Ki67染色实验结果同样显示circDVL1的高表达明显抑制肿瘤增殖。因此，通过本研究鉴定出肾癌发生发展密切相关的circDVL1和circMYH9，为肾透明细胞癌早期诊断以及Fuhrman分级提供新方法，为发展肾癌新疗法提供新靶点和研究方向。在基金的支持下，本研究共发表两篇SCI论文。