Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. The initial treatment of lung cancer depends on the definition of the tumor type and its staging. The most common treatment is chemotherapy, and the first-line treatment is a combination of carboplatin and paclitaxel. Although this treatment has good efficacy, there is a high prevalence of adverse events, particularly hematological reactions. Studies on new biomarkers related to these adverse events, such as circulating microRNAs (miRNAs/miRs), are important for optimizing the quality of life of patients. miRNAs have high stability in several biological fluids and they have specific expressions in different tissues or pathologies. Thus, the present study aimed to assess the relationship between circulating miRNAs and adverse hematologic reactions caused by treatment with carboplatin + paclitaxel in patients with lung cancer. Blood was collected from patients before and 15 days after chemotherapy for hematological adverse reaction analysis, microarray and quantitative (q)PCR validation. Adverse reactions were classified according to the Common Terminology Criteria for Adverse Events v4.0. Microarray analysis was performed using plasma from six patients without anemia and six patients with anemia, and nine miRNAs were differentially expressed. miR-1273g-3p, miR-3613-5p and miR-455-3p, identified using microarray, were assessed using qPCR in 20 patients without anemia and 26 patients with anemia. Bioinformatic analyses of miR-455-3p were performed using miRWalk, the Database for Annotation, Visualization and Integrated Discovery and GeneMania software. Microarray analysis of patients with and without anemia revealed nine significant differentially-expressed plasma miRNAs among these patients. Of these, miR-1273g-3p, miR-3613-5p and miR-455-3p were chosen for further assessment. Only miR-455-3p demonstrated a significant reduction in expression (P=0.04) between the groups before chemotherapy with carboplatin + paclitaxel. Bioinformatics analysis of miR-455-3p revealed a relationship between this miRNA and the hematopoietic pathway, particularly with respect to the RUNX family transcription factor 1 (RUNX1) and TAL bHLH transcription factor 1, erythroid differentiation factor (TAL1) genes. The most prevalent adverse reactions in patients with lung cancer treated with carboplatin + paclitaxel were hematological, particularly anemia. This adverse reaction, caused by dysfunction of the hematopoietic system, may be explained by a possible association between the important genes in this system, RUNX1 and TAL1, and hsa-miR-455-3p.

中文翻译：

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hsa-miR-455-3P 作为接受卡铂联合紫杉醇治疗的非小细胞肺癌患者贫血的预测生物标志物。

肺癌是全世界癌症相关发病率和死亡率的主要原因。肺癌的初始治疗取决于肿瘤类型的定义及其分期。最常见的治疗方法是化疗，一线治疗方法是卡铂和紫杉醇的组合。尽管这种治疗具有良好的疗效，但不良事件的发生率很高，特别是血液学反应。对与这些不良事件相关的新生物标志物（例如循环 microRNA (miRNA/miR)）的研究对于优化患者的生活质量非常重要。 miRNA在多种生物体液中具有高度稳定性，并且在不同组织或病理中具有特定表达。因此，本研究旨在评估肺癌患者中循环miRNA与卡铂+紫杉醇治疗引起的不良血液学反应之间的关系。在化疗前和化疗后 15 天从患者身上采集血液，用于血液学不良反应分析、微阵列和定量 (q)PCR 验证。不良反应根据不良事件通用术语标准 v4.0 进行分类。使用 6 名无贫血患者和 6 名贫血患者的血浆进行微阵列分析，发现 9 种 miRNA 存在差异表达。使用微阵列鉴定的 miR-1273g-3p、miR-3613-5p 和 miR-455-3p 通过 qPCR 对 20 名无贫血患者和 26 名贫血患者进行评估。使用 miRWalk、注释、可视化和集成发现数据库以及 GeneMania 软件对 miR-455-3p 进行生物信息分析。对患有和不患有贫血的患者进行的微阵列分析揭示了这些患者中九种显着差异表达的血浆 miRNA。其中，选择 miR-1273g-3p、miR-3613-5p 和 miR-455-3p 进行进一步评估。在卡铂 + 紫杉醇化疗前，各组之间仅 miR-455-3p 表达显着降低（P=0.04）。 miR-455-3p 的生物信息学分析揭示了该 miRNA 与造血途径之间的关系，特别是与 RUNX 家族转录因子 1 ( RUNX1 ) 和 TAL bHLH 转录因子 1、红细胞分化因子 ( TAL1 ) 基因有关。卡铂+紫杉醇治疗的肺癌患者最常见的不良反应是血液学不良反应，尤其是贫血。这种由造血系统功能障碍引起的不良反应可以通过该系统中的重要基因RUNX1和TAL1与 hsa-miR-455-3p 之间的可能关联来解释。