Disseminated tumour cells with highly aberrant genomes are linked to poor prognosis in operable oesophageal adenocarcinoma.
Disseminated tumour cells with highly aberrant genomes are linked to poor prognosis in operable oesophageal adenocarcinoma.
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具有高度异常基因组的传播肿瘤细胞与可手术食管腺癌的预后不良有关。
DOI：
10.1038/bjc.2017.233
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发表时间：
2017-08-22
影响因子：
8.8
通讯作者：
Möhlendick B
中科院分区：
文献类型：
--
作者：
Schumacher S;Bartenhagen C;Hoffmann M;Will D;Fischer JC;Baldus SE;Vay C;Fluegen G;Dizdar L;Vallböhmer D;Klein CA;Knoefel WT;Stoecklein NH;Möhlendick B
染色体不稳定性（CIN）已多次被确定为预后标志物。在这里，我们评估了从可手术食管腺癌（EAC）患者分离的单播散性肿瘤细胞（DTC）中每细胞异常基因组的百分比（PAG）作为CIN的衡量指标，以评估cin高DTC对预后的影响。我们从可手术EAC患者的骨髓（BM）或淋巴结（LN）制剂中分离出ck18阳性的dtc。全基因组扩增后，使用中期比较基因组杂交（mCGH）分析单个dtc的染色体增益和损失。在两个独立的EAC患者队列（队列1，n=44；队列2，n=29）中，我们计算了每个DTC的PAG，并通过STEPP（亚群体治疗效应模式图）分析确定了识别高危患者的临界阈值。在dtc中观察到的最常见的染色体改变是典型的EAC，但dtc在个体患者之间显示不同的PAG。一般来说，lndtc的PAG明显高于bmdtc。STEPP分析显示，在两个独立的EAC队列以及相应的合并分析中，dtc PAG的增加与短期生存风险的增加相关。在所有三个数据集（队列1、队列2和合并队列）中，paga高dtc是显著降低生存率的独立风险。孤立标记物阳性dtc的PAG/CIN分析可识别预后较差的可手术EAC患者，表明其存在更具侵袭性的微小残留疾病。
Chromosomal instability (CIN) has repeatedly been identified as a prognostic marker. Here we evaluated the percentage of aberrant genome per cell (PAG) as a measure of CIN in single disseminated tumour cells (DTC) isolated from patients with operable oesophageal adenocarcinoma (EAC), to assess the impact of CINhigh DTCs on prognosis. We isolated CK18positive DTCs from bone marrow (BM) or lymph node (LN) preparations of operable EAC patients. After whole-genome amplification, single DTCs were analysed for chromosomal gains and losses using metaphase-based comparative genomic hybridisation (mCGH). We calculated the PAG for each DTC and determined the critical threshold value that identifies high-risk patients by STEPP (Subpopulation Treatment Effect Pattern Plot) analysis in two independent EAC patient cohorts (cohort #1, n=44; cohort #2; n=29). The most common chromosomal alterations observed among the DTCs were typical for EAC, but the DTCs showed a varying PAG between individual patients. Generally, LNDTCs displayed a significantly higher PAG than BMDTCs. STEPP analysis revealed an increasing PAG of DTCs to be correlated with an increased risk for short survival in two independent EAC cohorts as well as in the corresponding pooled analysis. In all three data sets (cohort #1, cohort #2 and pooled cohort), PAGhigh DTCs conferred an independent risk for a significantly decreased survival. The analysis of PAG/CIN in solitary marker-positive DTCs identifies operable EAC patients with poor prognosis, indicating a more aggressive minimal residual disease.
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影响因子：
168.9
作者：
Klein, CA;Blankenstein, TJF;Riethmüller, G
通讯作者：
Riethmüller, G
影响因子：
3.7
作者：
Frankel, Adam;Armour, Nicola;Barbour, Andrew
通讯作者：
Barbour, Andrew
影响因子：
24.5
作者：
Goh, X. Y.;Rees, J. R. E.;Fitzgerald, R. C.
通讯作者：
Fitzgerald, R. C.
食管鳞状细胞癌的空间瘤内异质性和时间克隆进化
影响因子：
30.8
作者：
Hao, Jia-Jie;Lin, De-Chen;Dinh, Huy Q.;Mayakonda, Anand;Jiang, Yan-Yi;Chang, Chen;Jiang, Ye;Lu, Chen-Chen;Shi, Zhi-Zhou;Xu, Xin;Zhang, Yu;Cai, Yan;Wang, Jin-Wu;Zhan, Qi-Min;Wei, Wen-Qiang;Berrnan, Benjamin P.;Wang, Ming-Rong;Koeffler, H. Phillip
通讯作者：
Koeffler, H. Phillip
影响因子：
11.2
作者：
Dulak AM;Schumacher SE;van Lieshout J;Imamura Y;Fox C;Shim B;Ramos AH;Saksena G;Baca SC;Baselga J;Tabernero J;Barretina J;Enzinger PC;Corso G;Roviello F;Lin L;Bandla S;Luketich JD;Pennathur A;Meyerson M;Ogino S;Shivdasani RA;Beer DG;Godfrey TE;Beroukhim R;Bass AJ
通讯作者：
Bass AJ