Purpose: Recent data indicate that cDNA microarray gene expression profile of blood cells can reflect disease states and thus have diagnostic value. We tested the hypothesis that blood cell gene expression can differentiate between bladder cancer and other genitourinary cancers as well as between bladder cancer and healthy controls. Experimental Design: We used Affymetrix U133 Plus 2.0 GeneChip (Affymetrix, Santa Clara, CA) to profile circulating blood total RNA from 35 patients diagnosed with one of three types of genitourinary cancer [bladder cancer (n = 16), testicular cancer (n = 10), and renal cell carcinoma (n = 9)] and compared their cDNA profiles with those of 10 healthy subjects. We then verified the expression levels of selected genes from the Affymetrix results in a larger number of bladder cancer patients (n = 40) and healthy controls (n = 27).Results: Blood gene expression profiles distinguished bladder cancer patients from healthy controls and from testicular and renal cancer patients. Differential expression of a combined set of seven gene transcripts (insulin-like growth factor^binding protein 7, sorting nexin16, chondroitin sulfate proteoglycan 6, and cathepsin D, chromodomain helicase DNA-binding protein 2, nell-like 2, and tumor necrosis factor receptor superfamily member 7) was able to discriminate bladder cancer from control samples with a sensitivity of 83% (95% confidence interval, 67-93%) and a specificity of 93% (95% confidence interval, 76-99%).
Conclusion:We have shown that the gene expression profile of circulating blood cells can distinguish bladder cancer from other types of genitourinary cancer and healthy controls and can be used to identify novel blood markers for bladder cancer.
Blood cells communicate with cells and extracellular matrixesin almost all tissues and organs in the body. Such interactions can affect gene expression of the blood cells. Thus, it has been suggested that the gene expression profiles of circulating blood cells may reflect the presence of disease in the body (1). Microarray studies of disease have been based on RNA derived from biopsy/tissue samples. However, blood-based microarray studies have several major advantages over tissue-based assessments. Blood samples are less invasive, allow for a larger sample size, and make feasible repeated sampling to monitor disease progression.Several recent studies have shown that total RNA derived from circulating blood can distinguish between control subjects and patients with various disease types (2 -7). For example, analyses of blood-derived total RNA were able to differentiate between patients with cardiovascular disease and healthy controls (2). Blood-based microarrays also distinguish patients with chronic fatigue syndrome from healthy controls (4). This latter example is particularly noteworthy because this syndrome is not detectable by any existing laboratory tests, and it has been unclear whether it represents a unique disease.In this study, we test the hypothesis that analyses of blood cell -derive...