A signature of immune function genes associated with recurrence-free survival in breast cancer patients.
A signature of immune function genes associated with recurrence-free survival in breast cancer patients.
复制标题
DOI：
10.1007/s10549-011-1470-x
复制
发表时间：
2012-02
影响因子：
3.8
通讯作者：
Manjili, Masoud H.
中科院分区：
文献类型：
--
作者：
Ascierto, Maria Libera;Kmieciak, Maciej;Idowu, Michael O.;Manjili, Rose;Zhao, Yingdong;Grimes, Margaret;Dumur, Catherine;Wang, Ena;Ramakrishnan, Viswanathan;Wang, Xiang-Yang;Bear, Harry D.;Marincola, Francesco M.;Manjili, Masoud H.
关键词：
肿瘤浸润性免疫细胞的临床意义已在包括乳腺癌在内的多种人类癌症中报道。然而，肿瘤浸润性免疫细胞的分子特征及其在乳腺癌患者中的预后价值仍然难以捉摸。我们假设肿瘤部位的免疫功能基因的独特网络可以预测乳腺癌患者远处复发的低风险与高风险，而无论其肿瘤中ER，PR或HER-2/neu的状态如何。我们在一个肿瘤复发1-5年的乳腺癌患者与无复发生存期长达7年的乳腺癌患者的不同队列中进行了回顾性研究。在诊断时从冷冻的肿瘤标本中提取RNA，并进行微阵列分析和实时RT-PCR。石蜡包埋的组织也进行免疫组织化学染色。我们确定了参与B细胞发育的免疫功能基因网络、与同种异体移植排斥和自身免疫反应相关的干扰素信号传导、抗原呈递途径以及适应性和先天性免疫应答之间的串扰在无复发生存的患者中特异性上调。在299个基因中，发现包括B细胞应答基因的5个基因以>85%的准确度预测无复发存活。实时RT-PCR证实了5-基因预后特征，其不同于FDA批准的MammaPrint组的70-基因特征和Oncotype DX复发评分测定组。提示复发高危患者的新辅助免疫治疗可能通过诱导免疫功能基因的表达来降低肿瘤复发。
The clinical significance of tumor-infiltrating immune cells has been reported in a variety of human carcinomas including breast cancer. However, molecular signature of tumor-infiltrating immune cells and their prognostic value in breast cancer patients remain elusive. We hypothesized that a distinct network of immune function genes at the tumor site can predict a low risk versus high risk of distant relapse in breast cancer patients regardless of the status of ER, PR, or HER-2/neu in their tumors. We conducted retrospective studies in a diverse cohort of breast cancer patients with a 1–5 year tumor relapse versus those with up to 7 years relapse-free survival. The RNAs were extracted from the frozen tumor specimens at the time of diagnosis and subjected to microarray analysis and real-time RT-PCR. Paraffin-embedded tissues were also subjected to immunohistochemistry staining. We determined that a network of immune function genes involved in B cell development, interferon signaling associated with allograft rejection and autoimmune reaction, antigen presentation pathway, and cross talk between adaptive and innate immune responses were exclusively upregulated in patients with relapse-free survival. Among the 299 genes, five genes which included B cell response genes were found to predict with >85% accuracy relapse-free survival. Real-time RT-PCR confirmed the 5-gene prognostic signature that was distinct from an FDA-cleared 70-gene signature of MammaPrint panel and from the Oncotype DX recurrence score assay panel. These data suggest that neoadjuvant immunotherapy in patients with high risk of relapse may reduce tumor recurrence by inducing the immune function genes.
登录
查看更多内容
影响因子：
3.7
作者：
Khodarev NN;Roach P;Pitroda SP;Golden DW;Bhayani M;Shao MY;Darga TE;Beveridge MG;Sood RF;Sutton HG;Beckett MA;Mauceri HJ;Posner MC;Weichselbaum RR
通讯作者：
Weichselbaum RR
DOI：
10.4049/jimmunol.1000901
发表时间：
2010-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lechner MG;Liebertz DJ;Epstein AL
通讯作者：
Epstein AL
影响因子：
168.9
作者：
Wang, YX;Klijn, JGM;Foekens, JA
通讯作者：
Foekens, JA
影响因子：
30.8
作者：
Lundmark, Frida;Duvefelt, Kristina;Hillert, Jan
通讯作者：
Hillert, Jan
影响因子：
7.4
作者：
Wang E
通讯作者：
Wang E