KRAS mutations in tumor tissue and plasma by different assays predict survival of patients with metastatic colorectal cancer.
KRAS mutations in tumor tissue and plasma by different assays predict survival of patients with metastatic colorectal cancer.
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通过不同的检测，肿瘤组织和血浆中的 KRAS 突变可预测转移性结直肠癌患者的生存。
DOI：
10.1186/s13046-014-0104-7
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发表时间：
2014-12-10
期刊：
影响因子：
--
通讯作者：
Paradiso A
中科院分区：
文献类型：
--
作者：
Xu JM;Liu XJ;Ge FJ;Lin L;Wang Y;Sharma MR;Liu ZY;Tommasi S;Paradiso A
检测转移性结直肠癌（mCRC）患者不同生物标本中KRAS突变的最佳实验室检测方法以及这些基因改变的临床相关性仍存在疑问。我们在一个大型的单机构系列的mCRC患者中分析了KRAS状态的诊断预测相关性，通过两种不同的检测方法在肿瘤和血浆DNA中测定。DNA测序和肽核酸介导的聚合酶链反应钳（PNA-PCR）用于确定来自仅接受化疗的mCRC患者的416个肿瘤和242个匹配血浆DNA样本的KRAS状态。分析了不同试验和组织类型与结局的关系。PNA-PCR在检测KRAS突变方面比测序显著更敏感（41%对30%，p < 0.001）。KRAS突变在肿瘤组织中比在血浆中更频繁（测序，38%对17%，p < 0.001; PNA-PCR，47%对31%，p < 0.001）。KRAS突变患者的中位OS始终短于KRAS野生型患者，与检测的检测方法和组织无关;最大差异是通过PNA-PCR分析的血浆样本（KRAS突变vs.野生型：15.7 vs. 19.1个月，p = 0.009）。未观察到KRAS状态与其他结局之间的相关性。当同时考虑肿瘤和血浆结果时，组织/血浆KRAS阴性/阴性、组织/血浆KRAS不一致和组织/血浆KRAS阳性/阳性患者的中位OS分别为21.0、16.9和15.4个月（p = 0.008）。KRAS突变状态与mCRC患者的预后相关。肿瘤组织和血浆中的KRAS突变是不良结局的强预后标志物。本文的在线版本（doi：10.1186/s13046-014-0104-7）包含补充材料，可供授权用户使用。
The optimal laboratory assay for detecting KRAS mutations in different biospecimens from patients with metastatic colorectal cancer (mCRC), and the clinical relevance of these gene alterations is still in question. We analyzed the prognostic–predictive relevance of KRAS status, determined in tumor and plasma DNA by two different assays, in a large mono-institutional series of mCRC patients. DNA sequencing and peptide-nucleic-acid-mediated-polymerase chain reaction clamping (PNA-PCR) were used to determine KRAS status in 416 tumor and 242 matched plasma DNA samples from mCRC patients who received chemotherapy only. Relationships with outcomes were analyzed with respect to the different assays and tissue types. PNA-PCR was significantly more sensitive in detecting KRAS mutations than sequencing (41% vs. 30%, p < 0.001). KRAS mutations were more frequent in tumor tissue than in plasma (sequencing, 38% vs. 17%, p < 0.001; PNA-PCR, 47% vs. 31%, p < 0.001). Median OS was consistently shorter in KRAS-mutated patients than KRAS wild-type patients, independent from the assay and tissue tested; the largest difference was in plasma samples analyzed by PNA-PCR (KRAS mutated vs. wild-type: 15.7 vs. 19.1 months, p = 0.009). No association was observed between KRAS status and other outcomes. When tumor and plasma results were considered together, median OS in patients categorized as tissue/plasma KRAS negative/negative, tissue/plasma KRAS discordant, and tissue/plasma KRAS positive/positive were 21.0, 16.9 and 15.4 months, respectively (p = 0.008). KRAS mutation status is of prognostic relevance in patients with mCRC. KRAS mutations in both tumor tissue and plasma are a strong prognostic marker for poor outcomes. The online version of this article (doi:10.1186/s13046-014-0104-7) contains supplementary material, which is available to authorized users.
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DOI：
10.1186/1756-9966-30-111
发表时间：
2011-12-06
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Liu Y;Liu B;Li XY;Li JJ;Qin HF;Tang CH;Guo WF;Hu HX;Li S;Chen CJ;Liu B;Gao HJ;Liu XQ
通讯作者：
Liu XQ
影响因子：
4.1
作者：
Oh, Ji Eun;Lim, Hee Sun;Yoo, Nam Jin
通讯作者：
Yoo, Nam Jin
影响因子：
51.1
作者：
Linardou, Helena;Dahabreh, Issa J.;Murray, Samuel
通讯作者：
Murray, Samuel
影响因子：
50.5
作者：
Tougeron, D.;Lecomte, T.;Karayan-Tapon, L.
通讯作者：
Karayan-Tapon, L.
影响因子：
45.3
作者：
Allegra, Carmen J.;Jessup, J. Milburn;Schilsky, Richard L.
通讯作者：
Schilsky, Richard L.