Background:Pembrolizumab has recently emerged as a PD-1 blockade immunotherapy treatment for lung cancer. It is critical that such treatment strategies for lung cancer should be chosen not only on the basis of histopathological features and the expression of targetable cell surface proteins (such as PD-1), but should rather be selected based on other determinants of treatment success or risk factors for poor prognosis. One method to forecast cancer trajectory is the identification of biomolecular signatures such as microRNAs (miRNAs), non-protein-coding RNA molecules that play a regulatory role in gene expression by modulating the translation or stability of messenger RNA.Methods:To find out which miRNAs have an important influence on anti-PD-1 treatment outcomes, we evaluated miRNA levels in sera from 38 lung cancer patients undergoing 3 months of pembrolizumab treatment. We selected a panel of miRNAs previously shown to be involved in lung cancer or PD-1 signaling and performed qPCR analysis.Results:Overall, we observed a significant decrease in the levels of miR126-5p (4-fold), let-7a (5-fold), miR133a-3p (4-fold), miR3615 (2-fold), miR4516 (3-fold), miR16 (3-fold), miR34c-5p (2-fold), miR20b-5p (5-fold), miR106b-5p (5-fold), miR146a-5p (3-fold) and miR181b-5p (3-fold) in response to treatment indicating effectiveness of immunotherapy. Within our selected panel of miRNAs, we identified two markers relevant to cancer prognosis: miR-217, which is negatively associated with patient survival, and let-7a, which is positively associated with patient survival.Conclusions:Our findings suggest that circulating miRNAs can be used for future treatment evaluation and lung cancer prognosis, with potential as therapeutic targets.
背景：帕博利珠单抗作为一种PD-1阻断免疫疗法，近年来已成为肺癌治疗的新选择。此类肺癌治疗策略的选择不应仅基于组织病理学特征及可靶向细胞表面蛋白（如PD-1）的表达水平，更应结合影响治疗成败的其他决定因素或预后不良的风险指标进行综合判断。预测癌症进展轨迹的方法之一是识别生物分子标志物，例如微小RNA（miRNA）——这类非编码RNA分子通过调控信使RNA的翻译或稳定性，在基因表达中发挥重要调节作用。 方法：为探究哪些miRNA对PD-1阻断治疗效果具有重要影响，我们检测了38例接受帕博利珠单抗治疗3个月的肺癌患者血清中的miRNA水平。选取一组既往研究证实与肺癌或PD-1信号通路相关的miRNA，通过定量聚合酶链反应进行分析。 结果：总体而言，我们观察到治疗响应组中miR126-5p（4倍）、let-7a（5倍）、miR133a-3p（4倍）、miR3615（2倍）、miR4516（3倍）、miR16（3倍）、miR34c-5p（2倍）、miR20b-5p（5倍）、miR106b-5p（5倍）、miR146a-5p（3倍）和miR181b-5p（3倍）的表达水平显著下降，提示免疫治疗的有效性。在选定miRNA组中，我们鉴定出两个与癌症预后相关的标志物：与患者生存期呈负相关的miR-217，以及与患者生存期呈正相关的let-7a。 结论：本研究提示循环miRNA可作为未来治疗评估和肺癌预后的生物标志物，并具有成为治疗靶点的潜力。
肿瘤(癌症)患者之家