【佳學(xué)基因檢測】免疫、增殖和分子亞型在乳腺癌預(yù)后中的相互作用

基因檢測有必要做嗎—解答

研討基因檢測人員學(xué)科學(xué)習(xí)手冊《腫瘤靶向藥物的敏感性及有效性》《Genome Biol》在.?2013 Apr 29;14(4):R34.發(fā)表了一篇題目為《免疫、增殖和分子亞型在乳腺癌預(yù)后中的相互作用》腫瘤靶向藥物治療基因檢測臨床研究文章。該研究由Srikanth Nagalla,?Jeff W Chou,?Mark C Willingham,?Jimmy Ruiz,?James P Vaughn,?Purnima Dubey,?Timothy L Lash,?Stephen J Hamilton-Dutoit,?Jonas Bergh,?Christos Sotiriou,?Michael A Black,?Lance D Miller等完成。促進(jìn)了腫瘤的正確治療與個性化用藥的發(fā)展，進(jìn)一步強(qiáng)調(diào)了基因信息檢測與分析的重要性。

腫瘤靶向藥物及正確治療臨床研究內(nèi)容關(guān)鍵詞：

失巢凋亡,膠質(zhì)母細(xì)胞瘤,免疫療法,泛癌分析,干性指數(shù),腫瘤微環(huán)境

腫瘤靶向治療基因檢測臨床應(yīng)用結(jié)果

基因解碼基因檢測的研究介紹：指示腫瘤增殖能力和腫瘤免疫細(xì)胞相互作用的基因表達(dá)特征已成為乳腺癌基因解碼基因檢測的研究結(jié)果的主要生物學(xué)驅(qū)動預(yù)測因子。這些特征如何在生物學(xué)和預(yù)后基因解碼基因檢測的研究介紹下相互關(guān)聯(lián)仍有待澄清?；蚪獯a基因檢測的研究結(jié)果：為了研究增殖和免疫基因特征之間的關(guān)系，基因解碼基因檢測分析了一個綜合數(shù)據(jù)集，該數(shù)據(jù)集包含 1,954 個臨床注釋的乳腺腫瘤表達(dá)譜，隨機(jī)分為訓(xùn)練和測試集允許基因生存關(guān)聯(lián)的雙向發(fā)現(xiàn)和驗(yàn)證。分層聚類揭示了一大群具有已知免疫功能的無遠(yuǎn)處轉(zhuǎn)移存活相關(guān)基因，這些基因進(jìn)一步分為三個不同的免疫元基因，可能反映 B 細(xì)胞和/或漿細(xì)胞； T細(xì)胞和自然殺傷細(xì)胞；和單核細(xì)胞和/或樹突狀細(xì)胞。增殖元基因允許將病例分層為增殖三分位數(shù)。這些宏基因的預(yù)后強(qiáng)度主要局限于賊高增殖三分位數(shù)內(nèi)的腫瘤，盡管在中等和低增殖三分位數(shù)中觀察到內(nèi)在的亞型特異性差異。在高度增殖的腫瘤中，高三分位免疫宏基因表達(dá)等同于顯著降低轉(zhuǎn)移風(fēng)險(xiǎn)，而三分位免疫宏基因中任何一種低三分位表達(dá)的腫瘤盡管其他兩種宏基因的表達(dá)較高，但與預(yù)后不良相關(guān)?；蚪獯a基因檢測的研究結(jié)論：這些發(fā)現(xiàn)表明腫瘤部位多種免疫細(xì)胞類型之間的有效相互作用以增殖依賴性方式促進(jìn)長期抗轉(zhuǎn)移免疫。在高度增殖的腫瘤中出現(xiàn)了一部分有效的免疫應(yīng)答者，具有新的預(yù)后影響。

腫瘤發(fā)生與反復(fù)轉(zhuǎn)移國際數(shù)據(jù)庫描述：

Background:?Gene expression signatures indicative of tumor proliferative capacity and tumor-immune cell interactions have emerged as principal biology-driven predictors of breast cancer outcomes. How these signatures relate to one another in biological and prognostic contexts remains to be clarified.Results:?To investigate the relationship between proliferation and immune gene signatures, we analyzed an integrated dataset of 1,954 clinically annotated breast tumor expression profiles randomized into training and test sets to allow two-way discovery and validation of gene-survival associations. Hierarchical clustering revealed a large cluster of distant metastasis-free survival-associated genes with known immunological functions that further partitioned into three distinct immune metagenes likely reflecting B cells and/or plasma cells; T cells and natural killer cells; and monocytes and/or dendritic cells. A proliferation metagene allowed stratification of cases into proliferation tertiles. The prognostic strength of these metagenes was largely restricted to tumors within the highest proliferation tertile, though intrinsic subtype-specific differences were observed in the intermediate and low proliferation tertiles. In highly proliferative tumors, high tertile immune metagene expression equated with markedly reduced risk of metastasis whereas tumors with low tertile expression of any one of the three immune metagenes were associated with poor outcome despite higher expression of the other two metagenes.Conclusions:?These findings suggest that a productive interplay among multiple immune cell types at the tumor site promotes long-term anti-metastatic immunity in a proliferation-dependent manner. The emergence of a subset of effective immune responders among highly proliferative tumors has novel prognostic ramifications.