MALDI mass spectrometric imaging based identification of clinically relevant signals in prostate cancer using large-scale tissue microarrays
MALDI mass spectrometric imaging based identification of clinically relevant signals in prostate cancer using large-scale tissue microarrays
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DOI：
10.1002/ijc.28080
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发表时间：
2013-08-15
影响因子：
6.4
通讯作者：
Schlueter, Hartmut
中科院分区：
文献类型：
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作者：
Steurer, Stefan;Borkowski, Carina;Schlueter, Hartmut
为了鉴定前列腺癌中与临床病理参数和TMPRSS 2-ERG融合状态相关的分子特征，我们采用MALDI质谱成像（MSI）对前列腺癌组织微阵列（TMA）进行分析，该组织微阵列包含来自1，044名患者的福尔马林固定、石蜡包埋的组织样本，这些患者的临床随访数据可用。MSI分析揭示了15种不同的与上皮结构相关的质量/电荷（m/z）信号。这些信号与临床病理特征的比较揭示了与有利的肿瘤表型的统计学相关性，例如四种信号的低Gleason分级、早期pT分期或低Ki 67标记指数（LI（m/z 700，m/z 1，502，m/z 1，199和m/z 3，577），一个信号的高Ki 67 LI之间的联系（m/z 1，013）和一个信号与PSA复发时间延长的关系（m/z 1，502; p=0.0145）。多种信号与我们的癌症的ERG融合状态相关。15个上皮相关信号中的2个（包括m/z 1，013和m/z 1，502）与可检测的ERG表达相关，5个信号（m/z 644、678、1，044、3，086和3，577）与ERG阴性相关。这些观察结果与融合型和非融合型前列腺癌之间的实质性分子差异一致。在本研究中观察到的信号可以表征在TMPRSS 2-ERG融合的发展中起作用的分子，或者反映作为ERG激活的结果而被激活的途径。MSI和大规模TMA的组合反映了一种强大的方法，该方法能够基于与临床病理学和分子数据的关联立即优先考虑MSI信号。
To identify molecular features associated with clinico-pathological parameters and TMPRSS2-ERG fusion status in prostate cancer, we employed MALDI mass spectrometric imaging (MSI) to a prostate cancer tissue microarray (TMA) containing formalin-fixed, paraffin-embedded tissues samples from 1,044 patients for which clinical follow-up data were available. MSI analysis revealed 15 distinct mass per charge (m/z)-signals associated to epithelial structures. A comparison of these signals with clinico-pathological features revealed statistical association with favorable tumor phenotype such as low Gleason grade, early pT stage or low Ki67 labeling Index (LI) for four signals (m/z 700, m/z 1,502, m/z 1,199 and m/z 3,577), a link between high Ki67LI for one signal (m/z 1,013) and a relationship with prolonged time to PSA recurrence for one signal (m/z 1,502; p=0.0145). Multiple signals were associated with the ERG-fusion status of our cancers. Two of 15 epithelium-associated signals including m/z 1,013 and m/z 1,502 were associated with detectable ERG expression and five signals (m/z 644, 678, 1,044, 3,086 and 3,577) were associated with ERG negativity. These observations are in line with substantial molecular differences between fusion-type and non-fusion type prostate cancer. The signals observed in this study may characterize molecules that play a role in the development of TMPRSS2-ERG fusions, or alternatively reflect pathways that are activated as a consequence of ERG-activation. The combination of MSI and large-scale TMAs reflects a powerful approach enabling immediate prioritization of MSI signals based on associations with clinico-pathological and molecular data.