Extracellular Vesicles in Small Cell Lung Cancer Early Detection

小细胞肺癌早期检测中的细胞外囊泡

• 批准号: 10115627
• 负责人: Ly James Lee
• 金额: $ 49.65万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-20 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10115627
• 关键词: Address; Age; Bioinformatics; Biological Assay; Biological Markers; Biology; Biometry; Blinded; Blood; Blood Circulation; Body Fluids; Cancer Biology; Cancer Detection; Cancer Etiology; Cancer Hospital; Cancer Patient; Caring; Case-Control Studies; Cations; Cells; Cessation of life; Clinical; Combined Modality Therapy; Complex; Comprehensive Cancer Center; Data; Detection; Development; Diagnostic tests; Discipline; Disease; Doctor of Medicine; Doctor of Philosophy; Early Diagnosis; Frequencies; Generations; Goals; Heterogeneity; Homologous Gene; Human; Individual; Investigation; Knowledge; Light; Liquid substance; Malignant neoplasm of lung; Measurement; Messenger RNA; Methods; MicroRNAs; Modality; Molecular; Nanochip Analytical Device; Nanotechnology; Newly Diagnosed; Nodule; Non-Small-Cell Lung Carcinoma; Ohio; Patients; Plasma; Population; Prospective Studies; Proteomics; Protocols documentation; Publishing; Quantitative Reverse Transcriptase PCR; RNA; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; Review Literature; Risk; Sampling; Screening for cancer; Smoker; Smoking; Source; Survival Rate; Systems Biology; Technology; Testing; Transcript; Transketolase; United States; base; biochip; biomarker development; cancer care; cancer diagnosis; cancer subtypes; cancer therapy; case control; cohort; cost; differential expression; early detection biomarkers; effective therapy; extracellular vesicles; high risk; high risk population; human disease; improved outcome; innovation; interdisciplinary approach; lung cancer screening; lung small cell carcinoma; nanoengineering; nanoparticle; new therapeutic target; next generation sequencing; noninvasive diagnosis; novel; potential biomarker; prospective; prospective test; statistics; technology development; thyroid transcription factor 1; validation studies

PROJECT SUMMARY Lung cancer is the leading cause of cancer deaths worldwide. While the implementation of lung cancer screening for non-small cell lung cancer (NSCLC) subtypes has brought significant hope to this disease, very limited options exist for the early detection of small cell lung cancer (SCLC) SCLC carries a 5-year survival rate of only 7% and despite the development of novel targeted therapies and early detection for NSCLC, no such advances have been achieved in SCLC. A gap in our current approach to lung cancer detection and treatment has been that informative and reliable biomarkers for the detection and surveillance of lung cancer have remained elusive. MicroRNAs (miRNAs) have emerged as viable biomarkers in body fluids thus, providing an excellent means to achieve non-invasive assays for early cancer detection. Furthermore, miRNA expression in circulation appears to be compartment specific. While the majority of miRNAs are intracellular, a significant number of miRNAs have been observed outside of cells, including in various bodily fluids. The origin, applications and potential functionality of RNAs in circulation are the sources of intriguing questions. Obtaining a detailed RNA spectrum in plasma would shed some light on this matter. We have taken a multidisciplinary approach to the investigation of circulating RNA transcripts that integrates expertise in miRNA biology, nanoengineering, lung cancer and bioinformatics. We have developed a simple tethered Cationic Lipoplex Nanoparticle (tCLN) biochip with pre-loaded molecular beacons (MBs) in the lipoplex nanoparticles as probes to capture and detect targeted miRNAs and mRNAs in human plasma without any need of pre- or post-sample treatment. We have successfully demonstrated the ability to assess both exosomal miRNAs and mRNAs using both Next Generation Sequencing and our tCLN biochip in cohorts of control smokers and patients with early stage NSCLC. Our primary objectives are to extend these novel findings by (1) Test and validate the utility of measurement of ASCL1 and DLL3 in the early detection of SCLC in a retrospective and prospective study with network samples (2) Develop A Panel of Comprehensive EV RNA Candidates using nest generation sequencing and q-RT-PCR (3) Develop an optimized EV nanochip based RNA Classifier for early SCLC detection and (4) Validate the optimized EV RNA Classifier by using the multiplex TLN array biochips in independent, blinded case control studies at the OSU James Cancer Hospital and from the SCLC consortium.

项目概要 肺癌是全世界癌症死亡的主要原因。在实施肺癌 非小细胞肺癌（NSCLC）亚型的筛查给这种疾病带来了巨大的希望，非常 小细胞肺癌 (SCLC) 的早期检测选择有限 SCLC 的 5 年生存率 只有 7%，尽管开发了新的靶向疗法和 NSCLC 的早期检测，但还没有这样的 SCLC 已取得进展。我们当前的肺癌检测和治疗方法存在差距 用于肺癌检测和监测的信息丰富且可靠的生物标志物已经 仍然难以捉摸。 MicroRNA (miRNA) 已成为体液中可行的生物标志物，因此提供了一种 实现早期癌症检测的非侵入性检测的绝佳方法。此外，miRNA 表达 循环似乎是隔室特定的。虽然大多数 miRNA 都存在于细胞内，但 在细胞外，包括在各种体液中，已观察到大量 miRNA。起源， RNA 在循环中的应用和潜在功能是有趣问题的根源。获得 血浆中详细的 RNA 光谱将为解决这个问题提供一些线索。我们采取了多学科 整合了 miRNA 生物学专业知识的循环 RNA 转录本研究方法， 纳米工程、肺癌和生物信息学。我们开发了一种简单的系留阳离子脂质体 纳米颗粒 (tCLN) 生物芯片，在 lipoplex 纳米颗粒中预载分子信标 (MB) 作为探针 捕获并检测人血浆中的目标 miRNA 和 mRNA，无需任何前采样或后采样 治疗。我们已经成功证明了使用评估外泌体 miRNA 和 mRNA 的能力 下一代测序和我们的 tCLN 生物芯片在对照吸烟者和早期吸烟患者群体中的应用 阶段非小细胞肺癌。我们的主要目标是通过以下方式扩展这些新颖的发现：（1）测试和验证 在一项回顾性和前瞻性研究中测量 ASCL1 和 DLL3 在 SCLC 早期检测中的作用 网络样本 (2) 使用巢生成开发综合 EV RNA 候选者小组 测序和 q-RT-PCR (3) 为早期 SCLC 开发基于 EV 纳米芯片的优化 RNA 分类器 (4) 使用多重 TLN 阵列生物芯片验证优化的 EV RNA 分类器 俄勒冈州立大学詹姆斯癌症医院和 SCLC 联盟进行的独立、盲法病例对照研究。

项目成果

Malignant Pleural Effusion at Presentation in Patients with Small-Cell Lung Cancer.

小细胞肺癌患者出现恶性胸腔积液。

• 发表时间: 2019
• 作者: Shojaee, Samira;Singh, Inderjit;Solsky, Ian;Nana
• 通讯作者: Nana

Non-Coding RNA Editing in Cancer Pathogenesis.

癌症发病机制中的非编码 RNA 编辑。

• 发表时间: 2020-07-08
• 影响因子: 5.2
• 作者: Romano, Giulia;Saviana, Michela;Le, Patricia;Li, Howard;Micalo, Lavender;Nigita, Giovanni;Acunzo, Mario;Nana
• 通讯作者: Nana

Tissue and exosomal miRNA editing in Non-Small Cell Lung Cancer.

非小细胞肺癌中的组织和外泌体 miRNA 编辑。

• 发表时间: 2018-07-05
• 影响因子: 4.6
• 作者: Nigita, Giovanni;Distefano, Rosario;Veneziano, Dario;Romano, Giulia;Rahman, Mohammad;Wang, Kai;Pass, Harvey;Croce, Carlo M;Acunzo, Mario;Nana
• 通讯作者: Nana

MiR-124a Regulates Extracellular Vesicle Release by Targeting GTPase Rabs in Lung Cancer.

MiR-124a 通过靶向肺癌中的 GTPase Rabs 来调节细胞外囊泡释放。

• 发表时间: 2020
• 作者: Romano, Giulia;Nigita, Giovanni;Calore, Federica;Saviana, Michela;Le, Patricia;Croce, Carlo M;Acunzo, Mario;Nana
• 通讯作者: Nana

A biological function based biomarker panel optimization process.

基于生物功能的生物标志物组优化过程。

• 发表时间: 2019-05-14
• 影响因子: 4.6
• 作者: Lee, Min Young;Kim, Taek;Walters, Kathie;Wang, Kai
• 通讯作者: Wang, Kai