A Cell Proliferation Signature Is a Marker of Extremely Poor Outcome in a Subpopulation of Breast Cancer Patients

Abstract

Breast cancer comprises a group of distinct subtypes that despite having similar histologic appearances, have very different metastatic potentials. Being able to identify the biological driving force, even for a subset of patients, is crucially important given the large population of women diagnosed with breast cancer. Here, we show that within a subset of patients characterized by relatively high estrogen receptor expression for their age, the occurrence of metastases is strongly predicted by a homogeneous gene expression pattern almost entirely consisting of cell cycle genes (5-year odds ratio of metastasis, 24.0; 95% confidence interval, 6.0-95.5). Overexpression of this set of genes is clearly associated with an extremely poor outcome, with the 10-year metastasis-free probability being only 24% for the poor group, compared with 85% for the good group. In contrast, this gene expression pattern is much less correlated with the outcome in other patient subpopulations. The methods described here also illustrate the value of combining clinical variables, biological insight, and machine-learning to dissect biological complexity. Our work presented here may contribute a crucial step towards rational design of personalized treatment. (Cancer Res 2005; 65(10): 4059-66)

Expression of Late Cell Cycle Genes and an Increased Proliferative Capacity Characterize Very Early Relapse of Childhood Acute Lymphoblastic Leukemia

“…Remarkably, gene expression profiling has also identified recently an up-regulation of cell cycle and cell proliferation relevant genes in a distinct poor prognosis subgroup of patients in this tumor entity (31). In particular, there is a considerable overlap in genes or gene families (CCNB2, CDC45L, MAD2L1, KIF23, PTTG2, ORC6L, and KNSL6) identified between the current and the breast cancer study (31). Moreover, similar results have been obtained recently for aggressive neuroblastoma (32) and poor prognosis lung squamous cell carcinoma (33).…”

Identification of molecular markers and signaling pathway in endometrial cancer in Hong Kong Chinese women by genome-wide gene expression profiling

“…BUB1B is required for metaphase arrest in response to a lack of bipolar attachment. Overexpression of this protein is associated with a decrease in chromosomal stability and poor outcome in breast cancer patients (Warren et al, 2002;Dai et al, 2005). CDC20 is necessary for the degradation of an S-phase cyclin, which can antagonize APC activity (Harper 25 et al, 2002).…”

Mass Spectrometric Detection of Tissue Proteins in Plasma

“…3 In brief, this was accomplished by the use of a biotinylated hydrazide instead of a solid-phase hydrazide to label only the cell surface glycoproteins on live B and T lymphocytes in culture. After labeling, total membrane proteins were again isolated from the cells (14) and were then proteolyzed with trypsin.…”

“…Although gene expression array studies on cells and tissues have shown that such markers, or marker panels, do exist and can be associated with pathological changes in the disease and its prognoses (2,3), most tissues are not readily accessible for routine gene expression screening, and the affected tissue segments might be difficult to identify a priori.…”