Background Breast cancers contain a minority population of cancercells characterized by CD44 expression but low or undetectablelevels of CD24 (CD44+CD24–/low) that have higher tumorigeniccapacity than other subtypes of cancer cells.
Methods We compared the gene-expression profile of CD44+CD24–/lowtumorigenic breast-cancer cells with that of normal breast epithelium.Differentially expressed genes were used to generate a 186-gene"invasiveness" gene signature (IGS), which was evaluated forits association with overall survival and metastasis-free survivalin patients with breast cancer or other types of cancer.
Results There was a significant association between the IGSand both overall and metastasis-free survival (P<0.001, forboth) in patients with breast cancer, which was independentof established clinical and pathological variables. When combinedwith the prognostic criteria of the National Institutes of Health,the IGS was used to stratify patients with high-risk early breastcancer into prognostic categories (good or poor); among patientswith a good prognosis, the 10-year rate of metastasis-free survivalwas 81%, and among those with a poor prognosis, it was 57%.The IGS was also associated with the prognosis in medulloblastoma(P=0.004), lung cancer (P=0.03), and prostate cancer (P=0.01).The prognostic power of the IGS was increased when combinedwith the wound-response (WR) signature.
Conclusions The IGS is strongly associated with metastasis-freesurvival and overall survival for four different types of tumors.This genetic signature of tumorigenic breast-cancer cells waseven more strongly associated with clinical outcomes when combinedwith the WR signature in breast cancer.
Source Information
From the Departments of Internal Medicine (R.L., G.Y.C., P.D., M.F.C.) and Statistics (K.S.), University of Michigan, Ann Arbor; Oncomed Pharmaceuticals, Mountain View, CA (X.W., A.G., T.H., J.L.); the Stanford Institute for Stem Cell Biology and Regenerative Medicine, Palo Alto, CA (P.D., M.F.C.); and the Department of Genetics, Stanford University School of Medicine, Stanford, CA (G.S.). Drs. Liu and Wang contributed equally to this article, and Drs. Chen and Dalerba contributed equally to this article.
A Gene Signature in Breast Cancer
Bertucci F., Cervera N., Birnbaum D., Wennmalm K., Miller L. D., Bergh J., Woodward W. A., Lucci A., Cristofanilli M., the Advanced Research Center for Micrometastatic Disease , Clarke M. F., Liu R., Wang X.
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N Engl J Med 2007;
356:1887-1888, May 3, 2007.
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