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

基因檢測(cè)要多少錢—答案

在高峰論壇中腫瘤基因檢測(cè)位點(diǎn)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(xì)胞肺癌患者的異常啟動(dòng)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(cè)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(jìn)了腫瘤的正確治療與個(gè)性化用藥的發(fā)展，進(jìn)一步強(qiáng)調(diào)了基因信息檢測(cè)與分析的重要性。

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

非小細(xì)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(cè)臨床應(yīng)用結(jié)果

腫瘤甲基化基因檢測(cè)目的：腫瘤致病基因及甲基化基因檢測(cè)的研究的目的是探討腫瘤抑制基因高甲基化對(duì)非小細(xì)胞肺癌 (NSCLC) 患者的預(yù)后價(jià)值。實(shí)驗(yàn)設(shè)計(jì)：呼吸科基因檢測(cè)技術(shù)開發(fā)驗(yàn)證小組使用定量甲基化特異性 PCR檢測(cè)了 155 例非小細(xì)胞肺癌 (NSCLC) 患者腫瘤中 9 個(gè)基因的甲基化狀態(tài)。腫瘤基因解碼團(tuán)隊(duì)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(cè)試基因數(shù)之比）在腺癌中顯著高于（0.38 +/- 0.20）鱗狀細(xì)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(xiǎn)模型中，p16 甲基化與顯著較差的生存率相關(guān)[風(fēng)險(xiǎn)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(gè)月）明顯短于 p16 高甲基化患者（中位數(shù) = 62.5 個(gè)月；P = 0.0001，對(duì)數(shù)秩檢驗(yàn)）。 CDH1 或 TIMP3 基因的高甲基化與顯著更好的生存相關(guān)，風(fēng)險(xiǎn)比分別為 0.51（95% CI，0.29-0.90）和 0.59（95% CI，0.36-0.97）。這三個(gè)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(shì)（P = 0.0007）。結(jié)論：多個(gè)基因的高甲基化對(duì)NSCLC患者的生存率表現(xiàn)出顯著的差異影響。需要評(píng)估每個(gè)甲基化基因?qū)ι娴挠绊懀蕴峁┵\佳的預(yù)后價(jià)值。

腫瘤發(fā)生與反復(fù)轉(zhuǎn)移國(guó)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.