Plasma Based Protein Signatures Associated with Small Cell Lung Cancer.
Plasma Based Protein Signatures Associated with Small Cell Lung Cancer.
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DOI：
10.3390/cancers13163972
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发表时间：
2021-08-06
期刊：
影响因子：
5.2
通讯作者：
Hanash S
中科院分区：
文献类型：
--
作者：
Fahrmann JF;Katayama H;Irajizad E;Chakraborty A;Kato T;Mao X;Park S;Murage E;Rusling L;Yu CY;Cai Y;Hsiao FC;Dennison JB;Tran H;Ostrin E;Wilson DO;Yuan JM;Vykoukal J;Hanash S
小细胞肺癌（SCLC）通常出现在晚期，并且与高死亡率相关。然而，如果在早期诊断出局部疾病，则可以实现长期生存。在这项研究中，我们报告了一个全面的蛋白质组分析的情况下收集的血浆在诊断或诊断前的小细胞肺癌的目的是确定血液为基础的标志物与疾病的发病机制。我们的研究揭示了以致癌MYC和YAP 1的特征为中心的循环蛋白特征的发生，这些特征在SCLC诊断时和诊断前在病例的血浆中升高。我们进一步报告了几种蛋白质，特别是炎症标志物，在SCLC诊断前几年被鉴定为血浆中升高，这可能表明疾病风险增加。总之，我们的研究确定了几种与SCLC发展相关的新型循环蛋白，这些蛋白可能为早期检测提供实用性。小细胞肺癌（SCLC）与包括Myc家族基因和YAP 1在内的癌基因的过度表达以及肿瘤抑制基因的失活有关。我们对从15名新诊断的早期SCLC患者和15名SCLC诊断前的患者中收集的血浆进行了深入的蛋白质组分析，并将结果与30名匹配对照的血浆蛋白质组谱进行了比较，以确定反映疾病发病机制的特征的发生。与匹配对照组相比，新诊断病例中共有272种蛋白质升高（受试者工作特征曲线下面积（AUC）≥ 0.60），其中31种蛋白质在诊断前一年内采集的血浆中也升高（AUC ≥ 0.60）。对SCLC相关蛋白的免疫途径分析显示，致癌MYC和YAP 1的特征富集。交叉的蛋白质升高的情况下，血浆与蛋白质组学档案的条件培养基从17个小细胞肺癌细胞系产生了52个重叠的蛋白质，其特征在于YAP 1相关的签名的细胞骨架重排和上皮间质转化。在诊断前一年以上收集的样本中，炎症标志物占主导地位。我们的综合分析确定了与致癌驱动相关的早期SCLC中的新循环蛋白质特征。
Small-cell lung cancer (SCLC) typically presents at an advanced stage and is associated with high mortality. When diagnosed at an early stage with localized disease, long-term survival can, however, be achieved. In this study, we report a comprehensive proteomic profiling of case plasmas collected at the time of diagnosis or preceding diagnosis of SCLC with the objective of identifying blood-based markers associated with disease pathogenesis. Our study reveals the occurrence of circulating protein features centered on signatures of oncogenic MYC and YAP1 that were elevated in plasmas of cases at and before the time-of-diagnosis of SCLC. We further report several proteins, particularly inflammatory markers, that were identified as elevated in plasma several years prior to the diagnosis of SCLC and that may indicate increased risk of disease. In summary, our study identifies several novel circulating proteins associated with SCLC development that may offer utility for early detection. Small-cell-lung cancer (SCLC) is associated with overexpression of oncogenes including Myc family genes and YAP1 and inactivation of tumor suppressor genes. We performed in-depth proteomic profiling of plasmas collected from 15 individuals with newly diagnosed early stage SCLC and from 15 individuals before the diagnosis of SCLC and compared findings with plasma proteomic profiles of 30 matched controls to determine the occurrence of signatures that reflect disease pathogenesis. A total of 272 proteins were elevated (area under the receiver operating characteristic curve (AUC) ≥ 0.60) among newly diagnosed cases compared to matched controls of which 31 proteins were also elevated (AUC ≥ 0.60) in case plasmas collected within one year prior to diagnosis. Ingenuity Pathway analyses of SCLC-associated proteins revealed enrichment of signatures of oncogenic MYC and YAP1. Intersection of proteins elevated in case plasmas with proteomic profiles of conditioned medium from 17 SCLC cell lines yielded 52 overlapping proteins characterized by YAP1-associated signatures of cytoskeletal re-arrangement and epithelial-to-mesenchymal transition. Among samples collected more than one year prior to diagnosis there was a predominance of inflammatory markers. Our integrated analyses identified novel circulating protein features in early stage SCLC associated with oncogenic drivers.
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影响因子：
4.2
作者：
Aseervatham J
通讯作者：
Aseervatham J
影响因子：
5.3
作者：
Kubo E;Hasanova N;Fatma N;Sasaki H;Singh DP
通讯作者：
Singh DP
影响因子：
--
作者：
Jayachandran A;Anaka M;Prithviraj P;Hudson C;McKeown SJ;Lo PH;Vella LJ;Goding CR;Cebon J;Behren A
通讯作者：
Behren A
影响因子：
5.8
作者：
Lachmann, Alexander;Xu, Huilei;Ma'ayan, Avi
通讯作者：
Ma'ayan, Avi
DOI：
10.1093/jnci/djy126
发表时间：
2019-04-01
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Fahrmann JF;Bantis LE;Capello M;Scelo G;Dennison JB;Patel N;Murage E;Vykoukal J;Kundnani DL;Foretova L;Fabianova E;Holcatova I;Janout V;Feng Z;Yip-Schneider M;Zhang J;Brand R;Taguchi A;Maitra A;Brennan P;Max Schmidt C;Hanash S
通讯作者：
Hanash S