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TEP linc-GTF2H2-1、RP3-466P17.2 和 lnc-ST8SIA4-12 作为肺癌诊断和进展预测的新型生物标志物。

TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 as novel biomarkers for lung cancer diagnosis and progression prediction.

机构信息

Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Ji-Yan Road, Jinan, 250117, Shandong Province, People's Republic of China.

Department of Clinical Laboratory, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, Jiangsu, People's Republic of China.

出版信息

J Cancer Res Clin Oncol. 2021 Jun;147(6):1609-1622. doi: 10.1007/s00432-020-03502-5. Epub 2021 Jan 29.

Abstract

PURPOSE

Platelets contain a rich repertoire of RNA species, such as mRNAs and long non-coding RNAs. During the development of tumors, platelets are "educated" by cancer cells, altering their transcriptome and molecular content, thereby, tumor educated platelet (TEP) lncRNA profile has the potential to diagnose lung cancer. The current study was aimed to examine whether TEPs might be a potential biomarker for lung cancer.

METHODS

Platelet precipitation was obtained by low-speed centrifugation. TEP linc-GTF2H2-1, RP3-466P17.2, and lnc-ST8SIA4-12 were selected by lncRNA microarray and validated by qPCR in a large cohort of lung cancer patients and healthy donors. Besides, we analyzed the association of their expression levels with clinicopathological features.

RESULTS

TEP linc-GTF2H2-1 and RP3-466P17.2 were significantly downregulated, while lnc-ST8SIA4-12 was significantly upregulated in patients with lung cancer or with early-stage lung cancer as compared to healthy donors, possessing AUCs of 0.781, 0.788, 0.725 for lung cancer and 0.704, 0.771, 0.768 for early-stage lung cancer, respectively. Notably, their combination demonstrated the markedly elevated AUCs of 0.921 for lung cancer and 0.895 for early-stage lung cancer. Besides, the combination of TEP linc-GTF2H2-1 was capable to facilitate diagnostic efficiencies of CEA, Cyfra21-1, or NSE to distinguish advanced-stage lung cancer patients from early ones, with an AUC of 0.899 based on the integration of these four factors.

CONCLUSION

Our data suggested that lncRNAs sequestered in TEPs enabled blood-based lung cancer diagnosis and progression prediction.

摘要

目的

血小板含有丰富的 RNA 种类,如 mRNA 和长非编码 RNA。在肿瘤发展过程中,血小板被癌细胞“教育”,改变其转录组和分子含量,因此,肿瘤教育血小板(TEP)lncRNA 谱有可能诊断肺癌。本研究旨在探讨 TEP 是否可能成为肺癌的潜在生物标志物。

方法

通过低速离心获得血小板沉淀。通过 lncRNA 微阵列选择 TEP linc-GTF2H2-1、RP3-466P17.2 和 lnc-ST8SIA4-12,并通过 qPCR 在大量肺癌患者和健康供体中进行验证。此外,我们分析了它们的表达水平与临床病理特征的相关性。

结果

与健康供体相比,肺癌患者或早期肺癌患者的 TEP linc-GTF2H2-1 和 RP3-466P17.2 明显下调,而 lnc-ST8SIA4-12 明显上调,其 AUC 分别为 0.781、0.788、0.725 用于肺癌和 0.704、0.771、0.768 用于早期肺癌。值得注意的是,它们的组合显示出明显升高的 AUC 分别为 0.921 用于肺癌和 0.895 用于早期肺癌。此外,TEP linc-GTF2H2-1 的组合能够提高 CEA、Cyfra21-1 或 NSE 的诊断效率,以便将晚期肺癌患者与早期患者区分开来,基于这四个因素的整合,AUC 为 0.899。

结论

我们的数据表明,TEP 中分离的 lncRNAs 能够进行基于血液的肺癌诊断和进展预测。

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