Lung cancer remains one of the leading causes of cancer-related deaths worldwide. It is classified into two main histological groups: non-small cell lung cancer (NSCLC) and small cell lung cancer. Improving the outcome of cancer patients could be possible by enhancing the early diagnosis. In the current study, we evaluated the levels of three microRNAs - miR-21-5p, miR-155-5p, and miR-181a-5p in tumor (TT) vs adjacent normal tissue (NT), as well as their expression levels in plasma and extracellular vesicles (EVs) from plasma in lung squamous cell carcinoma (LUSC) male patients vs healthy individuals as means to identify a panel of miRNAs that could serve as novel biomarkers for the diagnosis of LUSC in male patients. Matched paired tissue samples from male LUSC (=40) patients were used for miRNA expression analysis. MiR-21-5p and miR-155-5p in tumor tissue were overexpressed, while underexpression of miR-181a-5p was observed in LUSC TT vs NT. These results were further validated in the TCGA LUSC dataset, considering 279 male samples. These alterations of miR-21-5p, miR-181a-5p, and miR-155-5p in tumor tissue are also present in plasma and plasma extracellular vesicles in LUSC male patients. In addition, ROC curves were performed to assess the sensitivity and specificity of different combinations of these miRNAs, confirming a high diagnostic accuracy for LUSC of up to 88 % in male subjects. The expression levels in tissue samples and the abundance in plasma and plasma EVs of the three miRNAs combined - miR-21-5p, miR-155-5p and miR-181a-5p – could be considered for further studies on biomarkers for the early detection of LUSC in male subjects.

中文翻译：

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男性 LUSC 患者的 miRNA 模式 - 三向镜像：组织、血浆和外泌体

肺癌仍然是全球癌症相关死亡的主要原因之一。它分为两个主要的组织学组：非小细胞肺癌（NSCLC）和小细胞肺癌。通过加强早期诊断可以改善癌症患者的治疗结果。在当前的研究中，我们评估了三种 microRNA - miR-21-5p、miR-155-5p 和 miR-181a-5p 在肿瘤 (TT) 与邻近正常组织 (NT) 中的水平，以及它们的表达水平比较肺鳞状细胞癌 (LUSC) 男性患者与健康个体的血浆和细胞外囊泡 (EV) 中的含量，作为鉴定一组 miRNA 的方法，这些 miRNA 可以作为诊断男性患者 LUSC 的新型生物标志物。来自男性 LUSC (=40) 患者的配对组织样本用于 miRNA 表达分析。与 NT 相比，LUSC TT 中肿瘤组织中的 miR-21-5p 和 miR-155-5p 过表达，而 miR-181a-5p 表达不足。这些结果在 TCGA LUSC 数据集中得到了进一步验证，考虑了 279 名男性样本。肿瘤组织中 miR-21-5p、miR-181a-5p 和 miR-155-5p 的这些改变也存在于 LUSC 男性患者的血浆和血浆细胞外囊泡中。此外，还进行了 ROC 曲线来评估这些 miRNA 不同组合的敏感性和特异性，证实了男性受试者中 LUSC 的诊断准确性高达 88%。组织样本中的表达水平以及血浆和血浆 EV 中三种 miRNA（miR-21-5p、miR-155-5p 和 miR-181a-5p）组合的丰度可考虑用于早期检测生物标志物的进一步研究男性受试者中的 LUSC。