Liu Rui, Wang Xinhao, Chen Grace Y, Dalerba Piero, Gurney Austin, Hoey Timothy, Sherlock Gavin, Lewicki John, Shedden Kerby, Clarke Michael F
Department of Internal Medicine, University of Michigan, Ann Arbor, USA.
N Engl J Med. 2007 Jan 18;356(3):217-26. doi: 10.1056/NEJMoa063994.
Breast cancers contain a minority population of cancer cells characterized by CD44 expression but low or undetectable levels of CD24 (CD44+CD24-/low) that have higher tumorigenic capacity than other subtypes of cancer cells.
We compared the gene-expression profile of CD44+CD24-/low tumorigenic 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 for its association with overall survival and metastasis-free survival in patients with breast cancer or other types of cancer.
There was a significant association between the IGS and both overall and metastasis-free survival (P<0.001, for both) in patients with breast cancer, which was independent of established clinical and pathological variables. When combined with the prognostic criteria of the National Institutes of Health, the IGS was used to stratify patients with high-risk early breast cancer into prognostic categories (good or poor); among patients with a good prognosis, the 10-year rate of metastasis-free survival was 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 combined with the wound-response (WR) signature.
The IGS is strongly associated with metastasis-free survival and overall survival for four different types of tumors. This genetic signature of tumorigenic breast-cancer cells was even more strongly associated with clinical outcomes when combined with the WR signature in breast cancer.
乳腺癌中存在一小部分癌细胞，其特征为表达CD44但CD24水平低或检测不到（CD44+CD24-/低），这些癌细胞比其他亚型的癌细胞具有更高的致瘤能力。
我们将CD44+CD24-/低致瘤性乳腺癌细胞的基因表达谱与正常乳腺上皮细胞的基因表达谱进行了比较。利用差异表达基因生成了一个186个基因的“侵袭性”基因特征（IGS），并评估其与乳腺癌或其他类型癌症患者的总生存期和无转移生存期的相关性。
IGS与乳腺癌患者的总生存期和无转移生存期均显著相关（两者P均<0.001），且独立于既定的临床和病理变量。当与美国国立卫生研究院的预后标准相结合时，IGS被用于将高危早期乳腺癌患者分层为预后类别（良好或不良）；在预后良好的患者中，10年无转移生存率为81%，在预后不良的患者中，为57%。IGS还与髓母细胞瘤（P=0.004）、肺癌（P=0.03）和前列腺癌（P=0.01）的预后相关。当与伤口反应（WR）特征相结合时，IGS的预后能力增强。
IGS与四种不同类型肿瘤的无转移生存期和总生存期密切相关。在乳腺癌中，这种致瘤性乳腺癌细胞的基因特征与伤口反应特征相结合时，与临床结局的相关性更强。
