Department of Medical Oncology, Chinese PLA General Hospital, Beijing 100853, P.R. China.
Mol Med Rep. 2019 Jan;19(1):441-451. doi: 10.3892/mmr.2018.9663. Epub 2018 Nov 19.
With a 5‑year survival rate of only 8%, pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer‑associated mortality worldwide. Unfortunately, even following radical surgery, patient outcomes remain poor. Emerging as a new class of biomarkers in human cancer, microRNAs (miRNAs/miRs) have been reported to have various tumor suppressor and oncogenic functions. In the present study, miRNA expression profiles of patients with PDAC and corresponding clinical data with survival profiles were obtained from The Cancer Genome Atlas database. A co‑expression network was constructed to detect the modules significantly associated with clinical features by weighted gene co‑expression network analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on the hub miRNAs in the module of interest for functional annotation. A prognosis model consisting of hub miRNAs was generated using the R package 'rbsurv' and validated in survival analysis. The expression data of 523 miRNAs in 124 patients with PDAC were analyzed in a co‑expression network. The turquoise module containing 131 miRNAs was identified to be associated with pathological T stage (cor=‑0.21; P=0.02). The 39 hub miRNAs of the turquoise module were then detected using the 'networkScreening' function in R. These miRNAs were predominantly involved in biological processes including 'regulation of transcription', 'apoptotic process', 'TGF‑β receptor signaling pathway', 'Ras protein signal transduction' and significantly enriched in 'cell cycle', 'adherens junction', 'FoxO', 'Hippo' and 'PI3K‑Akt signaling' pathways. A prognostic signature consisting of four hub miRNAs (miR‑1197, miR‑218‑2, miR‑889 and miR‑487a) associated with pathological T stage was identified to stratify the patients with early‑stage PDAC into high and low risk groups. The signature may serve as a potential prognostic biomarker for patients with early‑stage PDAC who undergo radical resection.
胰腺癌(PDAC)的 5 年生存率仅为 8%,是全球导致癌症相关死亡的第四大原因。不幸的是,即使进行了根治性手术,患者的预后仍然很差。microRNAs(miRNAs/miRs)作为人类癌症中的一类新型生物标志物,已被报道具有多种肿瘤抑制和致癌功能。本研究从癌症基因组图谱(TCGA)数据库中获取了 PDAC 患者的 miRNA 表达谱和相应的临床生存数据。通过加权基因共表达网络分析构建共表达网络,以检测与临床特征显著相关的模块。对感兴趣模块中的核心 miRNA 进行基因本体论和京都基因与基因组百科全书通路富集分析,以进行功能注释。使用 R 包“rbsurv”生成包含核心 miRNA 的预后模型,并在生存分析中进行验证。对 124 例 PDAC 患者的 523 个 miRNA 的表达数据进行了共表达网络分析。鉴定出包含 131 个 miRNA 的绿松石模块与病理 T 期相关(cor=‑0.21;P=0.02)。然后使用 R 中的“networkScreening”功能检测绿松石模块的 39 个核心 miRNA。这些 miRNA 主要参与了“转录调节”、“凋亡过程”、“TGF-β受体信号通路”、“Ras 蛋白信号转导”等生物学过程,并显著富集于“细胞周期”、“黏着连接”、“FoxO”、“Hippo”和“PI3K-Akt 信号”通路。鉴定出与病理 T 期相关的由四个核心 miRNA(miR-1197、miR-218-2、miR-889 和 miR-487a)组成的预后标志物,可将早期 PDAC 患者分为高危和低危组。该标志物可能成为接受根治性手术的早期 PDAC 患者的潜在预后生物标志物。
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