【摘要翻译】前列腺癌相关进展之二：前列腺癌的诊断方面
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1.基因表达谱鉴定前列腺癌临床亚型
Lapointe J, Li C, Higgins JP, van de Rijn M, Bair E, Montgomery K, Ferrari M, Egevad L, Rayford W, Bergerheim U, Ekman P, DeMarzo AM, Tibshirani R, Botstein D, Brown PO, Brooks JD, Pollack JR
Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):811-6
癌症中死亡率较高的前列腺癌的生物学行为涵盖很广，有的进展很缓慢，有的迅速进展成转移性疾病。为了探索该病临床表现差异的分子机制，研究人员用包含约 26000 个基因的 cDNA 微阵列测定了 62 个原位前列腺癌样本、 41 个正常前列腺样本和 9 个前列腺癌淋巴结转移样本的基因表达。根据基因表达的独特形式，无监督层次聚类方法可轻易区别肿瘤与正常组织，并且能确认出前列腺癌的三个亚型。前列腺癌的三个亚型中的两个与晚期癌症有关联。研究人员用免疫组化法分析了两个基因，这两个基因在不同肿瘤亚型的表达不同。一个是 MUC1 ，在进展迅速的肿瘤亚型高度表达，与复发风险增加有关（ P = 0.003 ）。另一个是 AZGP1 ，在其他肿瘤亚型高度表达，与复发风险减少有关（ P = 0.0008 ）。多变量分析表明， MUC1 和 AZGP1 染色是独立于肿瘤分期、术前前列腺特异性抗原（ PSA ）的预示肿瘤复发的因素。结果显示前列腺癌可按照基因表达模式进行分类。
Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):811-6. Epub 2004 Jan 7. Related Articles, Links
Gene expression profiling identifies clinically relevant subtypes of prostate cancer.
Lapointe J, Li C, Higgins JP, van de Rijn M, Bair E, Montgomery K, Ferrari M, Egevad L, Rayford W, Bergerheim U, Ekman P, DeMarzo AM, Tibshirani R, Botstein D, Brown PO, Brooks JD, Pollack JR.
Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Prostate cancer, a leading cause of cancer death, displays a broad range of clinical behavior from relatively indolent to aggressive metastatic disease. To explore potential molecular variation underlying this clinical heterogeneity, we profiled gene expression in 62 primary prostate tumors, as well as 41 normal prostate specimens and nine lymph node metastases, using cDNA microarrays containing approximately 26,000 genes. Unsupervised hierarchical clustering readily distinguished tumors from normal samples, and further identified three subclasses of prostate tumors based on distinct patterns of gene expression. High-grade and advanced stage tumors, as well as tumors associated with recurrence, were disproportionately represented among two of the three subtypes, one of which also included most lymph node metastases. To further characterize the clinical relevance of tumor subtypes, we evaluated as surrogate markers two genes differentially expressed among tumor subgroups by using immunohistochemistry on tissue microarrays representing an independent set of 225 prostate tumors. Positive staining for MUC1, a gene highly expressed in the subgroups with "aggressive" clinicopathological features, was associated with an elevated risk of recurrence (P = 0.003), whereas strong staining for AZGP1, a gene highly expressed in the other subgroup, was associated with a decreased risk of recurrence (P = 0.0008). In multivariate analysis, MUC1 and AZGP1 staining were strong predictors of tumor recurrence independent of tumor grade, stage, and preoperative prostate-specific antigen levels. Our results suggest that prostate tumors can be usefully classified according to their gene expression patterns, and these tumor subtypes may provide a basis for improved prognostication and treatment stratification.
Lapointe J, Li C, Higgins JP, van de Rijn M, Bair E, Montgomery K, Ferrari M, Egevad L, Rayford W, Bergerheim U, Ekman P, DeMarzo AM, Tibshirani R, Botstein D, Brown PO, Brooks JD, Pollack JR
Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):811-6
癌症中死亡率较高的前列腺癌的生物学行为涵盖很广，有的进展很缓慢，有的迅速进展成转移性疾病。为了探索该病临床表现差异的分子机制，研究人员用包含约 26000 个基因的 cDNA 微阵列测定了 62 个原位前列腺癌样本、 41 个正常前列腺样本和 9 个前列腺癌淋巴结转移样本的基因表达。根据基因表达的独特形式，无监督层次聚类方法可轻易区别肿瘤与正常组织，并且能确认出前列腺癌的三个亚型。前列腺癌的三个亚型中的两个与晚期癌症有关联。研究人员用免疫组化法分析了两个基因，这两个基因在不同肿瘤亚型的表达不同。一个是 MUC1 ，在进展迅速的肿瘤亚型高度表达，与复发风险增加有关（ P = 0.003 ）。另一个是 AZGP1 ，在其他肿瘤亚型高度表达，与复发风险减少有关（ P = 0.0008 ）。多变量分析表明， MUC1 和 AZGP1 染色是独立于肿瘤分期、术前前列腺特异性抗原（ PSA ）的预示肿瘤复发的因素。结果显示前列腺癌可按照基因表达模式进行分类。
Proc Natl Acad Sci U S A. 2004 Jan 20;101(3):811-6. Epub 2004 Jan 7. Related Articles, Links
Gene expression profiling identifies clinically relevant subtypes of prostate cancer.
Lapointe J, Li C, Higgins JP, van de Rijn M, Bair E, Montgomery K, Ferrari M, Egevad L, Rayford W, Bergerheim U, Ekman P, DeMarzo AM, Tibshirani R, Botstein D, Brown PO, Brooks JD, Pollack JR.
Department of Pathology, Stanford University, Stanford, CA 94305, USA.
Prostate cancer, a leading cause of cancer death, displays a broad range of clinical behavior from relatively indolent to aggressive metastatic disease. To explore potential molecular variation underlying this clinical heterogeneity, we profiled gene expression in 62 primary prostate tumors, as well as 41 normal prostate specimens and nine lymph node metastases, using cDNA microarrays containing approximately 26,000 genes. Unsupervised hierarchical clustering readily distinguished tumors from normal samples, and further identified three subclasses of prostate tumors based on distinct patterns of gene expression. High-grade and advanced stage tumors, as well as tumors associated with recurrence, were disproportionately represented among two of the three subtypes, one of which also included most lymph node metastases. To further characterize the clinical relevance of tumor subtypes, we evaluated as surrogate markers two genes differentially expressed among tumor subgroups by using immunohistochemistry on tissue microarrays representing an independent set of 225 prostate tumors. Positive staining for MUC1, a gene highly expressed in the subgroups with "aggressive" clinicopathological features, was associated with an elevated risk of recurrence (P = 0.003), whereas strong staining for AZGP1, a gene highly expressed in the other subgroup, was associated with a decreased risk of recurrence (P = 0.0008). In multivariate analysis, MUC1 and AZGP1 staining were strong predictors of tumor recurrence independent of tumor grade, stage, and preoperative prostate-specific antigen levels. Our results suggest that prostate tumors can be usefully classified according to their gene expression patterns, and these tumor subtypes may provide a basis for improved prognostication and treatment stratification.
