Vasselli James R, Shih Joanna H, Iyengar Shuba R, Maranchie Jodi, Riss Joseph, Worrell Robert, Torres-Cabala Carlos, Tabios Ray, Mariotti Andra, Stearman Robert, Merino Maria, Walther McClellan M, Simon Richard, Klausner Richard D, Linehan W Marston
Urologic Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):6958-63. doi: 10.1073/pnas.1131754100. Epub 2003 May 30.
To identify potential molecular determinants of tumor biology and possible clinical outcomes, global gene-expression patterns were analyzed in the primary tumors of patients with metastatic renal cell cancer by using cDNA microarrays. We used grossly dissected tumor masses that included tumor, blood vessels, connective tissue, and infiltrating immune cells to obtain a gene-expression "profile" from each primary tumor. Two patterns of gene expression were found within this uniformly staged patient population, which correlated with a significant difference in overall survival between the two patient groups. Subsets of genes most significantly associated with survival were defined, and vascular cell adhesion molecule-1 (VCAM-1) was the gene most predictive for survival. Therefore, despite the complex biological nature of metastatic cancer, basic clinical behavior as defined by survival may be determined by the gene-expression patterns expressed within the compilation of primary gross tumor cells. We conclude that survival in patients with metastatic renal cell cancer can be correlated with the expression of various genes based solely on the expression profile in the primary kidney tumor.
为了确定肿瘤生物学的潜在分子决定因素以及可能的临床结果,我们使用cDNA微阵列分析了转移性肾细胞癌患者原发肿瘤中的整体基因表达模式。我们使用大体解剖的肿瘤块,其中包括肿瘤、血管、结缔组织和浸润性免疫细胞,以从每个原发肿瘤中获得基因表达“谱”。在这个分期一致的患者群体中发现了两种基因表达模式,这与两个患者组之间的总生存期存在显著差异相关。定义了与生存最显著相关的基因子集,血管细胞黏附分子-1(VCAM-1)是最能预测生存的基因。因此,尽管转移性癌症具有复杂的生物学特性,但由生存定义的基本临床行为可能由原发大体肿瘤细胞集合中表达的基因表达模式决定。我们得出结论,转移性肾细胞癌患者的生存仅基于原发性肾肿瘤中的表达谱就可以与各种基因的表达相关联。