【佳學基因檢測】免疫、增殖和分子亞型在乳腺癌預后中的相互作用

基因檢測有必要做嗎—解答

研討基因檢測人員學科學習手冊《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。促進了腫瘤的正確治療與個性化用藥的發(fā)展，進一步強調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容關鍵詞：

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

腫瘤靶向治療基因檢測臨床應用結果

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胞相互作用的基因表達特征已成為乳腺癌基因解碼基因檢測的研究結果的主要生物學驅動預測因子。這些特征如何在生物學和預后基因解碼基因檢測的研究介紹下相互關聯仍有待澄清?；蚪獯a基因檢測的研究結果：為了研究增殖和免疫基因特征之間的關系，基因解碼基因檢測分析了一個綜合數據集，該數據集包含 1,954 個臨床注釋的乳腺腫瘤表達譜，隨機分為訓練和測試集允許基因生存關聯的雙向發(fā)現和驗證。分層聚類揭示了一大群具有已知免疫功能的無遠處轉移存活相關基因，這些基因進一步分為三個不同的免疫元基因，可能反映 B 細胞和/或漿細胞； T細胞和自然殺傷細胞；和單核細胞和/或樹突狀細胞。增殖元基因允許將病例分層為增殖三分位數。這些宏基因的預后強度主要局限于賊高增殖三分位數內的腫瘤，盡管在中等和低增殖三分位數中觀察到內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等同于顯著降低轉移風險，而三分位免疫宏基因中任何一種低三分位表達的腫瘤盡管其他兩種宏基因的表達較高，但與預后不良相關。基因解碼基因檢測的研究結論：這些發(fā)現表明腫瘤部位多種免疫細胞類型之間的有效相互作用以增殖依賴性方式促進長期抗轉移免疫。在高度增殖的腫瘤中出現了一部分有效的免疫應答者，具有新的預后影響。

腫瘤發(fā)生與反復轉移國際數據庫描述：

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.