*University of California, Los Angeles, AIDS Institute, Los Angeles, CA; Departments of †Obstetrics and Gynecology; ‡Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA; §Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA; ‖Department of Epidemiology, University of California, Los Angeles, Fielding School of Public Health, Los Angeles, CA; Departments of ¶Epidemiology; #Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; **Division of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL; and ††Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA.
J Acquir Immune Defic Syndr. 2014 Jun 1;66(2):229-37. doi: 10.1097/QAI.0000000000000146.
To determine if changes in levels of serum microRNAs (miRNAs) were seen preceding the diagnosis of AIDS-related non-Hodgkin lymphoma (AIDS-NHL).
Serum miRNA levels were compared in 3 subject groups from the Multicenter AIDS Cohort Study: HIV-negative men (n = 43), HIV-positive men who did not develop NHL (n = 45), and HIV-positive men before AIDS-NHL diagnosis (n = 62, median time before diagnosis, 8.8 months).
A total of 175 serum-enriched miRNAs were initially screened to identify differentially expressed miRNAs among these groups and the results validated by quantitative polymerase chain reaction. Receiver-operating characteristic analysis was then performed to assess biomarker utility.
Higher levels of miR-21 and miR-122, and a lower level of miR-223, were able to discriminate HIV-infected from the HIV-uninfected groups, suggesting that these miRNAs are biomarkers for HIV infection but are not AIDS-NHL specific. Among the HIV-infected groups, a higher level of miR-222 was able to discriminate diffuse large B-cell lymphoma (DLBCL) and primary central nervous system lymphoma (PCNSL) subjects from HIV-infected subjects who did not develop NHL, with area under the receiver-operating characteristic curve of 0.777 and 0.792, respectively. At miR-222 cutoff values of 0.105 for DLBCL and 0.109 for PCNSL, the sensitivity and specificity were 75% and 77%, and 80% and 82%, respectively.
Altered serum levels of miR-21, miR-122, and miR-223 are seen in HIV-infected individuals. Higher serum level of miR-222 has clear potential as a serum biomarker for earlier detection of DLBCL and PCNSL among HIV-infected individuals.
确定血清 microRNAs（miRNAs）水平的变化是否早于艾滋病相关非霍奇金淋巴瘤（AIDS-NHL）的诊断。
比较了来自多中心艾滋病队列研究的 3 组受试者的血清 miRNA 水平：HIV 阴性男性（n=43）、未发生 NHL 的 HIV 阳性男性（n=45）和 AIDS-NHL 诊断前的 HIV 阳性男性（n=62，中位数诊断前时间为 8.8 个月）。
最初筛选了 175 种血清富集 miRNA，以鉴定这些组之间差异表达的 miRNA，并通过定量聚合酶链反应验证结果。然后进行接收者操作特征分析以评估生物标志物的效用。
miR-21 和 miR-122 水平升高，miR-223 水平降低，可区分 HIV 感染与未感染人群，表明这些 miRNA 是 HIV 感染的生物标志物，但不是 AIDS-NHL 特异性的。在 HIV 感染组中，miR-222 水平升高可区分弥漫性大 B 细胞淋巴瘤（DLBCL）和原发性中枢神经系统淋巴瘤（PCNSL）患者与未发生 NHL 的 HIV 感染患者，受试者工作特征曲线下面积分别为 0.777 和 0.792。在 miR-222 截断值为 0.105 时用于 DLBCL 和 0.109 时用于 PCNSL，敏感性和特异性分别为 75%和 77%，80%和 82%。
在 HIV 感染个体中可见血清 miR-21、miR-122 和 miR-223 水平改变。血清 miR-222 水平升高具有作为 HIV 感染个体中更早检测 DLBCL 和 PCNSL 的血清生物标志物的明确潜力。
