The tumour hypoxia marker pimonidazole reflects a transcriptional programme associated with aggressive prostate cancer.
The tumour hypoxia marker pimonidazole reflects a transcriptional programme associated with aggressive prostate cancer.
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DOI：
10.1038/bjc.2014.604
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发表时间：
2015-01-20
影响因子：
8.8
通讯作者：
Lyng, H.
中科院分区：
文献类型：
--
作者：
Ragnum, H. B.;Vlatkovic, L.;Lie, A. K.;Axcrona, K.;Julin, C. H.;Frikstad, K. M.;Hole, K. H.;Seierstad, T.;Lyng, H.
缺氧标记物哌莫硝唑是癌症侵袭性的候选生物标记物。我们研究了前列腺癌中与哌莫硝唑染色相关的转录程序。通过图像引导对 52 名患者的研究队列进行索引肿瘤活检，其中 43 名患者在前列腺切除术前接受哌莫硝唑治疗。验证了 46 名 (88%) 患者的索引肿瘤内的活检位置，这些患者被纳入基因表达谱和免疫组织化学分析。使用分别包含 59 名和 281 名患者的两个独立队列进行验证。增殖、DNA 修复和缺氧反应中基因的表达是与哌莫硝唑染色相关的转录程序的主要部分。构建了 32 个必需基因的特征，并显示与 Ki67 染色呈正相关，证实了基因数据所表明的缺氧肿瘤中增殖的增加。还发现与肿瘤分期和淋巴结状态呈正相关，但与血液前列腺特异性抗原水平不呈正相关，这与哌莫硝唑染色的结果一致。与攻击性的关联在验证队列中得到证实，其中特征与格里森评分相关，并分别具有独立的预后影响。哌莫硝唑染色反映了前列腺癌的侵袭性缺氧表型，其特征是增殖、DNA 修复和缺氧反应基因的上调。
The hypoxia marker pimonidazole is a candidate biomarker of cancer aggressiveness. We investigated the transcriptional programme associated with pimonidazole staining in prostate cancer. Index tumour biopsies were taken by image guidance from an investigation cohort of 52 patients, where 43 patients received pimonidazole before prostatectomy. Biopsy location within the index tumour was verified for 46 (88%) patients, who were included for gene expression profiling and immunohistochemistry. Two independent cohorts of 59 and 281 patients were used for validation. Expression of genes in proliferation, DNA repair and hypoxia response was a major part of the transcriptional programme associated with pimonidazole staining. A signature of 32 essential genes was constructed and showed positive correlation to Ki67 staining, confirming the increased proliferation in hypoxic tumours as suggested from the gene data. Positive correlations were also found to tumour stage and lymph node status, but not to blood prostate-specific antigen level, consistent with the findings for pimonidazole staining. The association with aggressiveness was confirmed in validation cohorts, where the signature correlated with Gleason score and had independent prognostic impact, respectively. Pimonidazole staining reflects an aggressive hypoxic phenotype of prostate cancer characterised by upregulation of proliferation, DNA repair and hypoxia response genes.
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前列腺癌的基因表达谱揭示了多个分子途径在转移过程中的参与。
影响因子：
3.8
作者：
Chandran, Uma R.;Ma, Changqing;Dhir, Rajiv;Bisceglia, Michelle;Lyons-Weiler, Maureen;Liang, Wenjing;Michalopoulos, George;Becich, Michael;Monzon, Federico A.
通讯作者：
Monzon, Federico A.
影响因子：
3.8
作者：
Kim, Seung-Jin;Choi, Hojung;Kim, Eungseok
通讯作者：
Kim, Eungseok
影响因子：
4.8
作者：
Cai, Yuqi;Balli, David;Kalin, Tanya V.
通讯作者：
Kalin, Tanya V.
DOI：
10.1158/1078-0432.ccr-13-0542
发表时间：
2013-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Eustace A;Mani N;Span PN;Irlam JJ;Taylor J;Betts GN;Denley H;Miller CJ;Homer JJ;Rojas AM;Hoskin PJ;Buffa FM;Harris AL;Kaanders JH;West CM
通讯作者：
West CM
影响因子：
4.8
作者：
Gilkes, Daniele M.;Bajpai, Saumendra;Semenza, Gregg L.
通讯作者：
Semenza, Gregg L.