弗吉尼亞州立大學(xué)梅西癌癥中心的研究人員已發(fā)現(xiàn)一個(gè)新生物標(biāo)志物,，這個(gè)新生物標(biāo)志物與機(jī)體免疫系統(tǒng)相關(guān),，可預(yù)測乳腺癌病人復(fù)發(fā)風(fēng)險(xiǎn),。這個(gè)突破可能導(dǎo)致形成進(jìn)一步個(gè)性化乳腺癌護(hù)理的新遺傳測試,。
這項(xiàng)研究發(fā)表在期刊《乳腺癌研究與治療》（Breast Cancer Research and Treatment）上,，它是第一個(gè)用定位于腫瘤上的腫瘤浸潤免疫細(xì)胞來預(yù)測癌癥復(fù)發(fā)的研究,。用乳腺癌患者的組織樣本,，研究人員發(fā)現(xiàn)了與腫瘤浸潤免疫細(xì)胞相關(guān)的特異五基因標(biāo)簽,，它能精確地預(yù)測無復(fù)發(fā)存活。當(dāng)前,，有2個(gè)主要測試用于預(yù)測乳腺癌患者復(fù)發(fā)風(fēng)險(xiǎn),，即21基因檢測（Oncotype DX panel）和70種基因表達(dá)譜檢測（MammaPrint panel）。這兩種檢測都集中于腫瘤細(xì)胞主要表達(dá)的基因,。
"我們知道,，當(dāng)機(jī)體檢測到癌癥時(shí),，便引發(fā)免疫反應(yīng)，免疫系統(tǒng)細(xì)胞通常出現(xiàn)在腫瘤位置上,。" 這項(xiàng)研究的主要研究人員,、弗吉尼亞州立大學(xué)梅西癌癥中心微生物學(xué)與免疫學(xué)副教授D.V.M.博士說，"我們的測試不同于當(dāng)前使用的測試,，它通過尋找針對癌癥出現(xiàn)的生物學(xué)反應(yīng),，而不依賴于因?qū)嶋H癌癥細(xì)胞的基因表達(dá)。"
組織樣本收集自乳腺癌女性患者,，保存于美國梅西中心組織和數(shù)據(jù)采集分析核心（TDAAC）超過7年時(shí)間,。Manjili 說，"我們研究了17個(gè)患者的數(shù)據(jù),，這些患者中,，8個(gè)在5年內(nèi)復(fù)發(fā)，9個(gè)保持無癌癥至7年,。"5基因標(biāo)簽預(yù)測這些病人復(fù)發(fā)的準(zhǔn)確率大于85%,。
Manjili和他的團(tuán)隊(duì)接下來將研究更大量患者的組織樣本，以進(jìn)一步證實(shí)該研究中的發(fā)現(xiàn),。他們還打算在治療中乳腺癌病人的長期研究中測試他們的發(fā)現(xiàn)。
Manjili說："我們的發(fā)現(xiàn)能導(dǎo)致形成臨床試驗(yàn),，以測試在高復(fù)發(fā)風(fēng)險(xiǎn)的乳腺癌患者中使用免疫療法優(yōu)先于常規(guī)治療,，這里的免疫療法能起動患者免疫系統(tǒng)來阻止復(fù)發(fā)的可能，更象一個(gè)疫苗,。”（生物谷bioon.com)
doi:10.1007/s10549-011-1470-x
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A signature of immune function genes associated with recurrence-free survival in breast cancer patients.
Ascierto ML, Kmieciak M, Idowu MO, Manjili R, Zhao Y, Grimes M, Dumur C, Wang E, Ramakrishnan V, Wang XY, Bear HD, Marincola FM, Manjili MH.
Abstract 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.
