2012年8月30日 訊 /生物谷BIOON/ --年齡在18個(gè)月或以上的患有轉(zhuǎn)移性神經(jīng)母細(xì)胞瘤的兒童診斷時(shí)通常發(fā)現(xiàn),，腫瘤相關(guān)炎癥基因表達(dá)的提高似乎與預(yù)后不良相關(guān),，據(jù)8月27日在線發(fā)表在Journal of Clinical Oncology雜志上的一則研究證實(shí)。
洛杉磯兒童醫(yī)院Shahab Asgharzadeh, MD和他的同事研究與腫瘤相關(guān)炎癥細(xì)胞相關(guān)的基因是否與生存期有關(guān),。免疫組化對(duì)71例局部和轉(zhuǎn)移性神經(jīng)母細(xì)胞瘤的腫瘤相關(guān)巨噬細(xì)胞（TAMs）進(jìn)行了研究,。無(wú)進(jìn)展生存期的預(yù)測(cè)是基于對(duì)133例轉(zhuǎn)移性NBL-NAS患者體內(nèi)44個(gè)腫瘤和炎癥基因進(jìn)行評(píng)估后得出來(lái)的。
該研究結(jié)果在參加兩個(gè)額外研究中的9 1例高風(fēng)險(xiǎn)的腫瘤患者身上得到了驗(yàn)證,。研究人員觀察到TAMs浸潤(rùn)的增加局部腫瘤惡化成轉(zhuǎn)移性神經(jīng)母細(xì)胞瘤,。與患者在診斷時(shí)更年輕時(shí)相比，患者在診斷時(shí)年齡在18個(gè)月或以上時(shí),，炎癥相關(guān)基因的表達(dá)是增高的,。一種新型的準(zhǔn)確性的14個(gè)腫瘤分類基因得分高出百分之二十五是由于TAMs表達(dá)了其中5個(gè)基因。研究報(bào)告首次證實(shí)了瘤內(nèi)炎癥在轉(zhuǎn)移性神經(jīng)母細(xì)胞瘤中的作用,，并為轉(zhuǎn)移性NBL-NA兒童提供了一個(gè)有效的預(yù)后指標(biāo),。這項(xiàng)研究部分由安進(jìn)公司資助。（生物谷：Bioon.com）
doi:10.1200/JCO.2011.40.9169
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Clinical Significance of Tumor-Associated Inflammatory Cells in Metastatic Neuroblastoma
Shahab Asgharzadeh, Jill A. Salo, Lingyun Ji, André Oberthuer, Matthias Fischer, et al.
Purpose Children diagnosed at age ≥ 18 months with metastatic MYCN-nonamplified neuroblastoma (NBL-NA) are at high risk for disease relapse, whereas those diagnosed at age < 18 months are nearly always cured. In this study, we investigated the hypothesis that expression of genes related to tumor-associated inflammatory cells correlates with the observed differences in survival by age at diagnosis and contributes to a prognostic signature.
Methods Tumor-associated macrophages (TAMs) in localized and metastatic neuroblastomas (n = 71) were assessed by immunohistochemistry. Expression of 44 genes representing tumor and inflammatory cells was quantified in 133 metastatic NBL-NAs to assess age-dependent expression and to develop a logistic regression model to provide low- and high-risk scores for predicting progression-free survival (PFS). Tumors from high-risk patients enrolled onto two additional studies (n = 91) served as independent validation cohorts.
Results Metastatic neuroblastomas had higher infiltration of TAMs than locoregional tumors, and metastatic tumors diagnosed in patients at age ≥ 18 months had higher expression of inflammation-related genes than those in patients diagnosed at age < 18 months. Expression of genes representing TAMs (CD33/CD16/IL6R/IL10/FCGR3) contributed to 25% of the accuracy of a novel 14-gene tumor classification score. PFS at 5 years for children diagnosed at age ≥ 18 months with NBL-NA with a low- versus high-risk score was 47% versus 12%, 57% versus 8%, and 50% versus 20% in three independent clinical trials, respectively.
Conclusion These data suggest that interactions between tumor and inflammatory cells may contribute to the clinical metastatic neuroblastoma phenotype, improve prognostication, and reveal novel therapeutic targets.
