Transcriptome profiling of whole blood cells identifies PLEK2 and C1QB in human melanoma.
Transcriptome profiling of whole blood cells identifies PLEK2 and C1QB in human melanoma.
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DOI：
10.1371/journal.pone.0020971
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Fujita M
中科院分区：
文献类型：
--
作者：
Luo Y;Robinson S;Fujita J;Siconolfi L;Magidson J;Edwards CK;Wassmann K;Storm K;Norris DA;Bankaitis-Davis D;Robinson WA;Fujita M
开发分析方法来识别容易获得的体液中的生物标志物对于癌症患者的早期诊断和管理非常有价值。外周全血是“富含核酸”和“富含炎性细胞”的信息储存库，并且代表因癌细胞的存在而改变的全身过程。我们对黑色素瘤患者的全血细胞进行了转录组分析。为了克服与基于血液的转录组分析相关的挑战，我们使用了PAXgene™管和NuGEN Ovation™球蛋白减少系统。这些系统在微阵列中的组合使用导致在黑色素瘤患者血液中差异表达的78个独特基因的鉴定。其中，68个基因进行了进一步分析，通过定量逆转录酶PCR使用血液样品从45个新诊断的黑色素瘤患者（阶段I至IV）和50个健康对照个体。39个基因被证实在黑色素瘤患者的血液样品中差异表达。逐步logit分析选择了18个2基因的签名，区分黑色素瘤从健康对照。其中，由PLEK2和C1QB组成的2基因签名导致了正确分类93.3%黑色素瘤患者和90%健康对照的最佳结果。这两种基因在所有阶段的黑色素瘤患者的血液样本中均上调。使用血液分级的进一步分析表明，CD45−和CD45+群体分别负责PLEK2和C1QB表达水平的改变。目前的研究首次分析了恶性黑色素瘤的全血转录组生物标志物。PLEK2是对黑色素瘤患者进行分类的最强基因，其在CD45亚群中的表达说明了分析全血细胞对生物标志物研究的重要性。这项研究表明，血细胞的转录组分析可用于早期检测黑色素瘤和监测患者的残留疾病。
Developing analytical methodologies to identify biomarkers in easily accessible body fluids is highly valuable for the early diagnosis and management of cancer patients. Peripheral whole blood is a “nucleic acid-rich” and “inflammatory cell-rich” information reservoir and represents systemic processes altered by the presence of cancer cells. We conducted transcriptome profiling of whole blood cells from melanoma patients. To overcome challenges associated with blood-based transcriptome analysis, we used a PAXgene™ tube and NuGEN Ovation™ globin reduction system. The combined use of these systems in microarray resulted in the identification of 78 unique genes differentially expressed in the blood of melanoma patients. Of these, 68 genes were further analyzed by quantitative reverse transcriptase PCR using blood samples from 45 newly diagnosed melanoma patients (stage I to IV) and 50 healthy control individuals. Thirty-nine genes were verified to be differentially expressed in blood samples from melanoma patients. A stepwise logit analysis selected eighteen 2-gene signatures that distinguish melanoma from healthy controls. Of these, a 2-gene signature consisting of PLEK2 and C1QB led to the best result that correctly classified 93.3% melanoma patients and 90% healthy controls. Both genes were upregulated in blood samples of melanoma patients from all stages. Further analysis using blood fractionation showed that CD45− and CD45+ populations were responsible for the altered expression levels of PLEK2 and C1QB, respectively. The current study provides the first analysis of whole blood-based transcriptome biomarkers for malignant melanoma. The expression of PLEK2, the strongest gene to classify melanoma patients, in CD45− subsets illustrates the importance of analyzing whole blood cells for biomarker studies. The study suggests that transcriptome profiling of blood cells could be used for both early detection of melanoma and monitoring of patients for residual disease.
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影响因子：
64.8
作者：
Clark, EA;Golub, TR;Hynes, RO
通讯作者：
Hynes, RO
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V
影响因子：
5
作者：
Batliwalla, FM;Baechler, EC;Gregersen, PK
通讯作者：
Gregersen, PK
影响因子：
6.2
作者：
Byrnes, KR;Garay, J;Faden, AI
通讯作者：
Faden, AI
影响因子：
11.5
作者：
Jaeger, Jochen;Koczan, Dirk;Kunz, Manfred
通讯作者：
Kunz, Manfred