Pancreatic ductal adenocarcinoma (PDAC), a neoplasm of the gastrointestinal tract, is the most common pancreatic malignancy (90%) and the fourth highest cause of cancer mortality worldwide. Surgery intervention is currently the only strategy able to offer an advantage in terms of overall survival, but prognosis remains poor even for operated patients. Therefore, the development of robust biomarkers for early diagnosis and prognostic stratification in clinical practice is urgently needed. In this work, we investigated deregulated microRNAs (miRNAs) in tissues from PDAC patients with high (G3) or low (G2) histological grade and with (N+) or without (N−) lymph node metastases. miRNA expression profiling was performed by a comprehensive PCR array and subsequent validation by RT-qPCR. The results showed a significant increase in miR-1-3p, miR-31-5p, and miR-205-5p expression in G3 compared to G2 patients (**p< 0.01; ***p< 0.001; ***p< 0.001). miR-518d-3p upregulation and miR-215-5p downregulation were observed in N+ compared to N− patients. A statistical analysis performed using OncomiR program showed the significant involvement (p< 0.05) of two miRNAs (miR-31 and miR-205) in the histological grade of PDAC patients. Also, an expression analysis in PDAC patients showed that miR-31 and miR-205 had the highest expression at grade 3 compared with normal and other tumor grades. Overall, survival plots confirmed that the overexpression of miR-31 and miR-205 was significantly correlated with decreased survival in TCGA PDAC clinical samples. A KEGG pathway analysis showed that all three miRNAs are involved in the regulation of multiple pathways, including the Hippo signaling, adherens junction and microRNAs in cancer, along with several target genes. Based on in silico analysis and experimental validation, our study suggests the potential role of miR-1-3p, miR-31-5p, and miR-205-5p as useful clinical biomarkers and putative therapeutic targets in PDAC, which should be further investigated to determine the specific molecular processes affected by their aberrant expression.
胰腺导管腺癌（PDAC）作为消化道肿瘤，是最常见的胰腺恶性肿瘤（占90%），也是全球癌症相关死亡的第四大原因。目前手术干预是唯一能改善患者总生存期的治疗策略，但即使接受手术的患者预后仍然较差。因此，临床实践中亟需开发可靠的生物标志物用于早期诊断和预后分层。本研究通过对比分析组织学分级高（G3）与低（G2）、伴（N+）或不伴（N-）淋巴结转移的PDAC患者组织样本，探究其中异常表达的微小RNA（miRNA）。采用全面PCR阵列进行miRNA表达谱分析，并通过RT-qPCR进行验证。结果显示，与G2患者相比，G3患者中miR-1-3p、miR-31-5p和miR-205-5p表达显著升高（**p<0.01；***p<0.001；***p<0.001）；与N-患者相比，N+患者中miR-518d-3p表达上调而miR-215-5p表达下调。通过OncomiR程序进行的统计分析表明，两种miRNA（miR-31和miR-205）与PDAC患者的组织学分级显著相关（p<0.05）。在PDAC患者中的表达分析进一步显示，与正常组织及其他肿瘤分级相比，miR-31和miR-205在3级肿瘤中表达最高。生存曲线分析证实，在TCGA PDAC临床样本中，miR-31和miR-205的过表达与患者生存期缩短显著相关。KEGG通路分析表明，这三种miRNA均参与调控多条信号通路，包括Hippo信号通路、粘附连接及癌症中的microRNA通路，并涉及多个靶基因。基于生物信息学分析和实验验证，本研究提示miR-1-3p、miR-31-5p和miR-205-5p可能作为PDAC潜在的临床生物标志物和治疗靶点，需进一步研究其异常表达影响的具体分子机制。
Identification of Tissue miRNA Signatures for Pancreatic Ductal Adenocarcinoma
肿瘤(癌症)患者之家