Transcriptional profiling of peripheral blood mononuclear cells in pancreatic cancer patients identifies novel genes with potential diagnostic utility.
Transcriptional profiling of peripheral blood mononuclear cells in pancreatic cancer patients identifies novel genes with potential diagnostic utility.
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DOI：
10.1371/journal.pone.0017014
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发表时间：
2011-02-10
期刊：
影响因子：
3.7
通讯作者：
Batra SK
中科院分区：
文献类型：
--
作者：
Baine MJ;Chakraborty S;Smith LM;Mallya K;Sasson AR;Brand RE;Batra SK
众所周知，包括胰腺癌（PC）在内的许多恶性肿瘤具有通过间接下调启动有效免疫应答所必需的单核细胞机制来逃避免疫系统的能力。这种知识，结合外周血单核细胞的转录组已被证明在许多疾病，包括肾细胞癌的背景下被改变的事实，导致我们研究，如果任何这样的基因表达的改变存在于PC中，因为它可能具有诊断效用。采用全基因组cDNA微阵列技术对26例PC患者和33例健康对照者的PBMC进行分析。在PC和健康对照组之间，发现383个基因存在显著差异，其中65个基因的表达变化至少为1.5倍。通路分析显示，这些基因中的许多落入负责造血分化、细胞因子信号传导和自然杀伤（NK）细胞和CD 8 + T细胞细胞毒性应答的通路中。无监督分层聚类分析确定了一个由SSBP 2、Ube 2b-rs 1、CA 5 B、F5、TBC 1D 8、ANXA 3、ARG 1和ADAMTS 20组成的八基因预测集，该预测集可以区分PC患者和健康对照，在来自未经治疗患者的盲态样本子集中的准确性为79%，灵敏度为83%，特异性为75%。总之，我们报告了PC患者和健康对照者PBMC的全球基因表达谱的首次深入比较。我们还确定了一个基因预测集，可以进一步开发用于PC中的诊断算法。未来的研究方向应包括分析慢性胰腺炎患者PBMC的表达谱，以及增加早期患者的数量，以评估PBMC在PC早期诊断中的效用。
It is well known that many malignancies, including pancreatic cancer (PC), possess the ability to evade the immune system by indirectly downregulating the mononuclear cell machinery necessary to launch an effective immune response. This knowledge, in conjunction with the fact that the trancriptome of peripheral blood mononuclear cells has been shown to be altered in the context of many diseases, including renal cell carcinoma, lead us to study if any such alteration in gene expression exists in PC as it may have diagnostic utility. PBMC samples from 26 PC patients and 33 matched healthy controls were analyzed by whole genome cDNA microarray. Three hundred eighty-three genes were found to be significantly different between PC and healthy controls, with 65 having at least a 1.5 fold change in expression. Pathway analysis revealed that many of these genes fell into pathways responsible for hematopoietic differentiation, cytokine signaling, and natural killer (NK) cell and CD8+ T-cell cytotoxic response. Unsupervised hierarchical clustering analysis identified an eight-gene predictor set, consisting of SSBP2, Ube2b-rs1, CA5B, F5, TBC1D8, ANXA3, ARG1, and ADAMTS20, that could distinguish PC patients from healthy controls with an accuracy of 79% in a blinded subset of samples from treatment naïve patients, giving a sensitivity of 83% and a specificity of 75%. In summary, we report the first in-depth comparison of global gene expression profiles of PBMCs between PC patients and healthy controls. We have also identified a gene predictor set that can potentially be developed further for use in diagnostic algorithms in PC. Future directions of this research should include analysis of PBMC expression profiles in patients with chronic pancreatitis as well as increasing the number of early-stage patients to assess the utility of PBMCs in the early diagnosis of PC.
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影响因子：
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作者：
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发表时间：
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影响因子：
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作者：
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