血清piRNAs差异表达谱在胃癌诊断及转移预测中的应用研究

piRNAs are small non-coding RNAs similar to miRNAs, different from long non-coding RNAs, not easily degraded and can easily pass through the cell membrane. An increasing number of studies have shown that aberrant piRNA expression is a signature feature across multiple tumor types and has the potential as a tumor maker; however, the expression of piRNAs in serum of tumor patients and its potential clinical utilities remain unclear.. In our preliminary experiments, a 7-piRNA panel for the diagnosis of GC (gastric cancer) has been developed by high-throughput sequencing and RT-qPCR. In our further studies, we will construct the model for GC diagnosis based on serum piRNA signatures using Support Vector Machine（SVM）combined with logistic regression. We will also analyze of the serum piRNA signatures in GC with or without lymphatic metastasis using the same methods and construct a prediction model for lymph node metastasis. In addition, we will identify key piRNAs that are consistently and differentially altered both in serum and tumor tissue, and explore the mechanisms underlying their roles in tumor carcinogenesis and metastasis of GC in vitro. Our study will help improve cancer diagnosis, preoperative prediction of lymph node metastasis and establish individualized tailored therapy for GC.

piRNAs是一类新型非编码小RNA，与microRNAs功能类似，能够在转录后水平介导基因沉默及调节肿瘤进展。最新研究表明，piRNAs在多种肿瘤组织中具有特异性表达谱并具备充当肿瘤标志物的潜能，但其在肿瘤患者中的血清学价值尚未明确。课题组前期通过高通量测序及RT-qPCR技术，初步获得了由7个piRNAs分子组成的胃癌血清piRNAs特异性表达谱，现拟运用支持向量机（SVM）并结合logistic回归分析，建立基于血清piRNAs差异表达谱的胃癌诊断模型；同时运用上述方法，分析“有”和“无”淋巴结转移两组胃癌血清piRNAs差异表达谱，建立胃癌转移预测模型；最后通过临床组织检测及胃癌细胞系体外实验，探讨相关piRNAs在胃癌发生发展中的作用。本研究将为胃癌的无创诊断及术前转移预测提供依据，并可初步揭示piRNAs在胃癌发生发展中的作用机制。

寻找新型生物标志物用于胃癌的早期诊断，及对患者术前淋巴结状态的精确评估，对于提高胃癌根治率、选择合理的手术方式及预后评估等均具有重要临床意义。本项目研究内容主要包括三个方面：(1）血清差异表达piRNAs作为无创肿瘤标志物的挖掘及临床价值分析；(2）关键piRNAs分子功能分析；(3）基于非编码小RNA标志物的肿瘤诊断、淋巴结转移预测及预后模型的构建。本项目通过高通量测序及RT-qPCR方法，筛选、鉴定了用于无创诊断胃癌及预测淋巴结转移的血清piRNAs标志物，对其临床应用价值进行了系统分析，同时选取关键piRNA分子，探讨其参与胃癌发生发展的相关机制。此外，本项目执行期间，在一定程度上对研究内容加以深化和延伸，挖掘相关非编码小RNA，用于构建胃肠肿瘤诊断、预后及淋巴结转移预测的可视化统计模型。我们最终发现了用于胃癌诊断及淋巴结转移预测的piRNAs标志物分子，初步探讨了关键分子的功能机制，并构建了肿瘤诊断、淋巴结转移预测及预后模型。相关研究成果在《Molecular Oncology》、《Aging》、《EbioMedicine》、《Cancer Management and Research》等期刊上发表。本研究可为精准医疗趋势下临床患者个体化治疗提供有利依据。