【佳學(xué)基因檢測】非小細胞肺癌患者的異常啟動子甲基化譜及其與生存的關(guān)聯(lián)

基因檢測要多少錢—答案

在高峰論壇中腫瘤基因檢測位點的全面性與正確性了解《Clin Cancer Res》在.?2006 Dec 15;12(24):7329-38.發(fā)表了一篇題目為《非小細胞肺癌患者的異常啟動子甲基化譜及其與生存的關(guān)聯(lián)》腫瘤靶向藥物治療基因檢測臨床研究文章。該研究由Jian Gu?,?David Berman,?Charles Lu,?Ignacio I Wistuba,?Jack A Roth,?Marsha Frazier,?Margaret R Spitz,?Xifeng Wu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(diào)了基因信息檢測與分析的重要性。

腫瘤轉(zhuǎn)移惡化的基因根源臨床研究內(nèi)容關(guān)鍵詞：

非小細胞肺癌,NSCLC,甲基化,肺腺癌,肺磷癌,老年患者,年輕患者

腫瘤靶向治療基因檢測臨床應(yīng)用結(jié)果

腫瘤甲基化基因檢測目的：腫瘤致病基因及甲基化基因檢測的研究的目的是探討腫瘤抑制基因高甲基化對非小細胞肺癌 (NSCLC) 患者的預(yù)后價值。實驗設(shè)計：呼吸科基因檢測技術(shù)開發(fā)驗證小組使用定量甲基化特異性 PCR檢測了 155 例非小細胞肺癌 (NSCLC) 患者腫瘤中 9 個基因的甲基化狀態(tài)。腫瘤基因解碼團隊分析了基因甲基化狀態(tài)與患者總體存活率之間的關(guān)聯(lián)。腫瘤基因序列變化及甲基化影響的研究結(jié)果：甲基化指數(shù)（定義為甲基化基因數(shù)與測試基因數(shù)之比）在腺癌中顯著高于（0.38 +/- 0.20）鱗狀細胞癌 (0.30 +/- 0.22; P = 0.027)，老年患者的腫瘤 (0.37 +/- 0.20) 比年輕患者 (0.30 +/- 0.22; P = 0.040)高，重度吸煙者的腫瘤 (0.39 +/- 0.21) 比輕度吸煙者 (0.29 +/- 0.20; P = 0.042)的甲基化比例高。在 Cox 比例風(fēng)險模型中，p16 甲基化與顯著較差的生存率相關(guān)[風(fēng)險比，1.95； 95% 置信區(qū)間 (95% CI), 1.21-3.39]。 Kaplan-Meier 生存曲線顯示，p16 高甲基化患者的生存期（中位數(shù) = 21.7 個月）明顯短于 p16 高甲基化患者（中位數(shù) = 62.5 個月；P = 0.0001，對數(shù)秩檢驗）。 CDH1 或 TIMP3 基因的高甲基化與顯著更好的生存相關(guān)，風(fēng)險比分別為 0.51（95% CI，0.29-0.90）和 0.59（95% CI，0.36-0.97）。這三個基因的聯(lián)合分析顯示，隨著不利事件數(shù)量的增加，生存率下降的顯著趨勢（P = 0.0007）。結(jié)論：多個基因的高甲基化對NSCLC患者的生存率表現(xiàn)出顯著的差異影響。需要評估每個甲基化基因?qū)ι娴挠绊?，以提供賊佳的預(yù)后價值。

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

Purpose:?The aim of this study was to investigate the prognostic value of hypermethylation of tumor suppressor genes in patients with non-small cell lung cancer (NSCLC).Experimental design:?We examined the methylation status of nine genes in 155 tumors from patients with NSCLC using quantitative methylation-specific PCR. We analyzed the associations between gene methylation status and overall patient survival.Results:?The methylation index, defined as the ratio between the number of methylated genes and the number of genes tested, was significantly higher in adenocarcinomas (0.38 +/- 0.20) than in squamous cell carcinomas (0.30 +/- 0.22; P = 0.027), in tumors from older patients (0.37 +/- 0.20) than younger patients (0.30 +/- 0.22; P = 0.040), and in tumors from heavier smokers (0.39 +/- 0.21) than lighter smokers (0.29 +/- 0.20; P = 0.042). In the Cox proportional hazards model, p16 methylation was associated with significantly poorer survival [hazard ratio, 1.95; 95% confidence interval (95% CI), 1.21-3.39]. Kaplan-Meier survival curves showed that patients with hypermethylated p16 had significantly shorter survival (median = 21.7 months) than patients without p16 hypermethylation (median = 62.5 months; P = 0.0001, log-rank test). Hypermethylation of CDH1 or TIMP3 gene was associated with significantly better survival with hazard ratios of 0.51 (95% CI, 0.29-0.90) and 0.59 (95% CI, 0.36-0.97), respectively. Joint analysis of these three genes showed a significant trend for poorer survival as the number of unfavorable events increased (P = 0.0007).Conclusion:?Hypermethylation of multiple genes exhibited significant differential effect on NSCLC patient survival. Assessment of the effect of each methylated gene on survival is needed to provide optimal prognostic value.