Alterations in microRNA (miRNA) expression have been reported in different cancers. We assessed the expression of 754 oncology–related miRNAs in esophageal adenocarcinoma (EAC) samples and evaluated their correlations with clinical parameters. We found that miR–221 and 483–3p were consistently upregulated in EAC patients vs. controls (Wilcoxon signed–rank test: miR–221p< 0.0001; miR–483–3pp< 0.0001). Kaplan–Meier analysis showed worse cancer–related survival among all EAC patients expressing high miR–221 or miR–483–3p levels (log–rankp= 0.0025 andp= 0.0235, respectively). Higher miR–221 or miR–483–3p levels also correlated with advanced tumor stages (Mann–Whitneyp= 0.0195 andp= 0.0085, respectively), and overexpression of miR–221 was associated with worse survival in low–risk EAC patients. Moreover, a significantly worse outcome was associated with the combined overexpression of miR–221 and miR–483–3p (log–rankp= 0.0410). To identify target genes affected by miRNA overexpression, we transfected the corresponding mimic RNA (miRVANA) for either miR–221 or miR–483–3p in a well–characterized esophageal adenocarcinoma cell line (OE19) and performed RNA–seq analysis. In the miRNA–overexpressing cells, we discovered a convergent dysregulation of genes linked to apoptosis, ATP synthesis, angiogenesis, and cancer progression, including a long non–coding RNA associated with oncogenesis, i.e., MALAT1. In conclusion, dysregulated miRNA expression, especially overexpression of miR–221 and 483–3p, was found in EAC samples. These alterations were connected with a lower cancer–specific patient survival, suggesting that these miRNAs could be useful for patient stratification and prognosis.
已有研究报道多种癌症中存在微小RNA（miRNA）表达异常。本研究检测了食管腺癌（EAC）样本中754种肿瘤相关miRNA的表达水平，并评估其与临床参数的相关性。结果显示，与对照组相比，miR-221和miR-483-3p在EAC患者中持续高表达（Wilcoxon符号秩检验：miR-221 p<0.0001；miR-483-3p p<0.0001）。Kaplan-Meier分析表明，在所有EAC患者中，高表达miR-221或miR-483-3p的患者癌症相关生存率更差（对数秩检验p值分别为0.0025和0.0235）。较高的miR-221或miR-483-3p水平还与晚期肿瘤分期相关（Mann-Whitney检验p值分别为0.0195和0.0085），且在低风险EAC患者中，miR-221的过表达与较差的生存率相关。此外，miR-221与miR-483-3p的联合过表达与显著更差的预后相关（对数秩检验p=0.0410）。为明确miRNA过表达影响的靶基因，我们在特征明确的食管腺癌细胞系（OE19）中分别转染miR-221或miR-483-3p的模拟RNA（miRVANA），并进行RNA测序分析。在miRNA过表达的细胞中，我们发现与凋亡、ATP合成、血管生成及癌症进展相关的基因出现趋同性失调，包括与肿瘤发生相关的长链非编码RNA MALAT1。综上所述，EAC样本中存在miRNA表达失调，特别是miR-221和miR-483-3p的过表达。这些改变与患者较低的癌症特异性生存率相关，提示这两种miRNA可能有助于患者分层和预后评估。
miRNA–221 and miRNA–483–3p Dysregulation in Esophageal Adenocarcinoma
肿瘤(癌症)患者之家