Integration of Biomarker Signatures from Peripheral Blood for Diagnosis, Prognosis, Remission and Recurrence of Lung Cancer

整合外周血生物标志物特征用于肺癌的诊断、预后、缓解和复发

• 批准号: 10376913
• 负责人: Qin Liu
• 金额: $ 44.82万
• 依托单位: WISTAR INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10376913
• 关键词: Acetyl-CoA C-Acetyltransferase; Affect; Algorithms; Aryl Hydrocarbon Hydroxylases; Benign; Biological Assay; Blood; Blood specimen; CXCR4 gene; Cancer Patient; Cancer Prognosis; Cells; Ceramides; Classification; Clinical; Coenzyme A; Collection; Data; Data Set; Deoxyguanosine kinase; Detection; Development; Diagnosis; Diagnostic; Disease remission; Early Diagnosis; Erythroid; Excision; FDA approved; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Genes; Goals; Hypoxia; Immune system; Immunologics; Individual; KLRB1 gene; Lung; Lung Neoplasms; Lung nodule; Maintenance; Malignant - descriptor; Malignant neoplasm of lung; Medical; Messenger RNA; Methods; MicroRNAs; Mitochondria; Mixed Function Oxygenases; Myelogenous; Myeloid Cells; NK cell receptor NKB1; Natural Killer Cells; Neoplasm Circulating Cells; Nodule; Non-Small-Cell Lung Carcinoma; Outcome; Patients; Peripheral Blood Mononuclear Cell; Process; Prognosis; RNA; Recurrence; Research; Research Personnel; Risk; Sampling; Sensitivity and Specificity; Signal Transduction; Site; Smoking; Smoking History; Source; Specificity; Survival Rate; System; T-Lymphocyte; Testing; Training; Transcriptional Regulation; Translating; Tumor Antigens; Vitamin D; X-Ray Computed Tomography; base; biomarker signature; cancer cell; cancer stem cell; cancer testis antigen; ceramide kinase; design; diagnostic biomarker; diagnostic platform; exosome; fitness; follow-up; genetic signature; improved; innovation; low dose computed tomography; lung cancer screening; malignant breast neoplasm; mortality; nano-string; novel; peripheral blood; predictive marker; predictive signature; prognostic signature; public health relevance; sample collection; screening; screening program; statistics; success; tumor

 DESCRIPTION (provided by applicant): The National lung Screening Trial has demonstrated that a 20% reduction in lung cancer mortality is associated with routine LDCT screening of older individuals with a heavy smoking history, but of the patients that had a positive screen for lung cancer based on lung nodules detected, approximately 96% proved to be false positives. These statistics highlight two unmet medical needs required to maximize the diagnostic potential of LDCT: 1) the development of diagnostic platforms that will distinguish malignant from benign nodules identified by routine LDCT, and 2) the development of inexpensive, non-invasive methods that can identify at risk individuals who would benefit from follow up with LDCT. The proposed research in Project 1 capitalizes on technical advances for assaying gene expression and abundant prior evidence that tumors are highly interactive with the immune system. Our previous studies demonstrated that it is possible to diagnose early-stage lung cancer with 90% sensitivity and 80% specificity using gene expression signatures from PBMC. The proposed research translates the PBMC diagnostic to a more clinically viable sample collection platform with the additional goal of increasing accuracy and assessing immunological processes affected by the presence or removal of a lung tumor. We present preliminary studies that support the hypothesis that this can be done. We have enriched the signature development process by assessing both mRNA and miRNA expression profiles to assess complimentary mechanisms for regulating gene expression and will also integrate Natural Killer cell and Myeloid cell markers associated with prognosis. We also introduce in Project 2 an assay for tumor associated antigens, the cancer testis antigens (CTAs) also associated with circulating tumor cells, cancer cell derived exosomes or other potentially important cells such as cancer stem cells. We provide strong preliminary evidence that detection of the mRNA for the CTA AKAP4 in PBMC derived RNA is possible and that detection is very highly correlated with the verified presence of a lung tumor. Strong preliminary results are presented for both projects. We also propose to integrate and expand the signatures from these 2 studies and assess accuracy on a single reliable platform that can assess both mRNA and miRNA expression, and is already FDA approved for a breast cancer prognosis signature, the nCounter from Nanostring.

 描述（由适用提供）：国家肺筛查试验表明，肺癌死亡率降低了20％与常规的LDCT筛查相关的较重吸烟史的老年人的常规LDCT筛查，但基于检测到的肺癌的肺癌阳性筛查的患者，大约96％的肺癌证明是虚假的阳性。这些统计数据突出了最大化LDCT诊断潜力所需的两种未满足的医疗需求：1）诊断平台的发展，这些平台将使恶性与常规LDCT鉴定的良性结节区分开，以及2）开发廉价的，非侵入性方法，这些方法可以从LDCT中识别受益于随访的风险个人。项目1中的拟议研究利用了测定基因表达的技术进步，并且绝对先前的证据证明肿瘤与免疫系统高度相互作用。我们先前的研究表明，使用PBMC的基因表达特征，可以诊断出具有90％敏感性和80％特异性的早期肺癌。拟议的研究将PBMC诊断转化为更临床上可行的样品收集平台，其其他目标是提高准确性并评估受肺部肿瘤存在或去除影响的免疫过程。我们提出了支持可以做到的假设的初步研究。我们通过评估mRNA和miRNA表达谱来评估确定基因表达的免费机制，从而丰富了签名开发过程，还将整合与预后相关的天然杀伤细胞和髓样细胞标记。我们还在项目2中引入了肿瘤相关抗原的测定，癌睾丸抗原（CTA）也与循环肿瘤细胞，癌细胞衍生的外泌体或其他潜在重要的细胞（如癌症干细胞）相关。我们提供了有力的初步证据，表明在PBMC衍生的RNA中检测mRNA是CTA AKAP4的检测，并且该检测与肺肿瘤的验证存在非常高度相关。两个项目都提出了强大的初步结果。我们还建议在单个可靠的平台上整合和扩展可以评估mRNA和miRNA表达的单个可靠平台上的签名，并已经被FDA批准用于乳腺癌预后签名，即来自纳米构成的NCOUNTER。

项目成果

Clinical presentation of COVID-19 - a model derived by a machine learning algorithm.

• DOI: 10.1515/jib-2020-0050
• 发表时间: 2021-03-04
• 期刊: Journal of integrative bioinformatics
• 影响因子: 1.9
• 作者: Yousef M;Showe LC;Ben Shlomo I
• 通讯作者: Ben Shlomo I

Recursive Cluster Elimination based Rank Function (SVM-RCE-R) implemented in KNIME.

• DOI: 10.12688/f1000research.26880.2
• 发表时间: 2020
• 期刊: F1000Research
• 作者: Yousef M;Bakir-Gungor B;Jabeer A;Goy G;Qureshi R;C Showe L
• 通讯作者: C Showe L

PAF-R on activated T cells: Role in the IL-23/Th17 pathway and relevance to multiple sclerosis.

• DOI: 10.1016/j.imbio.2020.152023
• 发表时间: 2020-11
• 期刊: Immunobiology
• 影响因子: 2.8
• 作者: A. Midgley;D. Barakat;M. Braitch;C. Nichols;Mihailo Nebozhyn;L. Edwards;S. Fox;B. Gran;R. Robins;L. Showe;C. Constantinescu

Lack of Atorvastatin Effect on Monocyte Gene Expression and Inflammatory Markers in HIV-1-infected ART-suppressed Individuals at Risk of non-AIDS Comorbidities.

• DOI: 10.20411/pai.v6i2.461
• 发表时间: 2021
• 期刊: Pathogens & immunity
• 作者: Yadav A;Kossenkov AV;Showe LC;Ratcliffe SJ;Choi GH;Montaner LJ;Tebas P;Shaw PA;Collman RG
• 通讯作者: Collman RG