Sim Jongmin, Kim Yeseul, Kim Hyunsung, Shin Su-Jin, Kim Dong-Hoon, Paik Seung Sam, Jang Kiseok
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine Department of Pathology, Hanyang University College of Medicine Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Medicine (Baltimore). 2018 Jun;97(25):e10996. doi: 10.1097/MD.0000000000010996.
Lung cancer is the most common cause of cancer-associated death worldwide. Postoperative relapse and subsequent metastasis result in a high mortality rate, even in early stage lung cancer. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level and are frequently dysregulated in various cancers. The aim of this study was to identify recurrence-associated miRNAs in early stage lung cancer. To screen for differentially expressed miRNAs related to postoperative recurrence, miRNA microarray data derived from stage I lung adenocarcinoma formalin-fixed paraffin-embedded (FFPE) tissue samples (n = 6) and publically available the Cancer Genome Atlas (TCGA) data were analyzed. An independent sample (n = 29) was used to validate candidate miRNAs by quantitative real-time polymerase chain reaction (qRT-PCR). In miRNA expression profiling, we identified 60 significantly dysregulated miRNAs in the relapsed group. Additionally, 20 dysregulated miRNAs were found using TCGA data set. Three miRNAs (let-7g-5p, miR-143-3p, and miR-374a-5p) were associated with postoperative recurrence in both microarray and TCGA data sets. All 3 candidate miRNAs were validated in the independent cohort of stage I adenocarcinoma by qRT-PCR. We discovered 3 recurrence-associated miRNAs of stage I lung adenocarcinoma samples using FFPE tissue, which showed possible clinical utility as biomarkers predicting recurrence after curative surgery. Further investigation of the functional properties of these miRNAs is needed.
肺癌是全球癌症相关死亡的最常见原因。即使是早期肺癌，术后复发及随后的转移也会导致高死亡率。微小RNA（miRNA）是一类小的非编码RNA，在转录后水平调节基因表达，且在各种癌症中经常失调。本研究的目的是鉴定早期肺癌中与复发相关的miRNA。为了筛选与术后复发相关的差异表达miRNA，我们分析了来自I期肺腺癌福尔马林固定石蜡包埋（FFPE）组织样本（n = 6）的miRNA微阵列数据以及公开可用的癌症基因组图谱（TCGA）数据。使用独立样本（n = 29）通过定量实时聚合酶链反应（qRT-PCR）验证候选miRNA。在miRNA表达谱分析中，我们在复发组中鉴定出60个显著失调的miRNA。此外，使用TCGA数据集发现了20个失调的miRNA。在微阵列和TCGA数据集中，三种miRNA（let-7g-5p、miR-143-3p和miR-374a-5p）与术后复发相关。通过qRT-PCR在I期腺癌独立队列中验证了所有3种候选miRNA。我们使用FFPE组织发现了I期肺腺癌样本中3种与复发相关的miRNA，它们作为预测根治性手术后复发的生物标志物显示出可能的临床应用价值。需要进一步研究这些miRNA的功能特性。
