Host chemokine signature as a biomarker for the detection of pre-cancerous cervical lesions.
Host chemokine signature as a biomarker for the detection of pre-cancerous cervical lesions.
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DOI：
10.18632/oncotarget.24946
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发表时间：
2018-04-06
期刊：
影响因子：
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通讯作者：
Cuschieri K
中科院分区：
文献类型：
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作者：
Bhatia R;Kavanagh K;Stewart J;Moncur S;Serrano I;Cong D;Cubie HA;Haas JG;Busby-Earle C;Williams ARW;Howie SEM;Cuschieri K
由于越来越多地采用hrHPV检测进行初级宫颈筛查，因此区分哪些hrHPV感染易患重大疾病的能力变得更加紧迫。理想情况下，感染的风险分层器或“分诊”应该是客观的，并且适合于考虑到筛查规模的自动化。CCL2、CCL3、CCL4、CXCL1、CXCL8和CXCL12是检测基础疾病[宫颈上皮内瘤变2级或更差（CIN2+）]的最强候选生物标志物。对于CIN2+，CCL2的曲线下面积（AUC）最高，为0.722，特异性为82%。一个由六种趋化因子CCL2、CCL3、CCL4、CXCL1、CXCL8和CXCL12组成的组合生物标志物组提供了71%的灵敏度和67%的特异性。目前的工作表明，五种趋化因子蛋白的水平是潜在疾病的指标。我们证明了基于趋化因子的生物标志物面板的技术可行性和有前途的临床性能，相当于其他分诊选项。现在有必要在纵向系列中进行进一步评估。使用人趋化因子蛋白质组学阵列试剂盒研究了一组31种趋化因子在常规采集的存档和前瞻性宫颈液基细胞学（LBC）样本中的表达。在Luminex平台上使用Procartaplex测定进一步验证了9种趋化因子。
The ability to distinguish which hrHPV infections predispose to significant disease is ever more pressing as a result of the increasing move to hrHPV testing for primary cervical screening. A risk-stratifier or “triage” of infection should ideally be objective and suitable for automation given the scale of screening. CCL2, CCL3, CCL4, CXCL1, CXCL8 and CXCL12 emerged as the strongest, candidate biomarkers to detect underlying disease [cervical intraepithelial neoplasia grade 2 or worse (CIN2+)]. For CIN2+, CCL2 had the highest area under the curve (AUC) of 0.722 with a specificity of 82%. A combined biomarker panel of six chemokines CCL2, CCL3, CCL4, CXCL1, CXCL8, and CXCL12 provides a sensitivity of 71% and specificity of 67%. The present work demonstrates that the levels of five chemokine-proteins are indicative of underlying disease. We demonstrate technical feasibility and promising clinical performance of a chemokine-based biomarker panel, equivalent to that of other triage options. Further assessment in longitudinal series is now warranted. A panel of 31 chemokines were investigated for expression in routinely taken archived and prospective cervical liquid based cytology (LBC) samples using Human Chemokine Proteomic Array kit. Nine chemokines were further validated using Procartaplex assay on the Luminex platform.