发现预测乳腺癌进展的生物标记

Risk For Invasive Breast Cancer Predicted By Biomarkers Years Before The Tumor Develops
生物标记可以在肿瘤发生前的数年前预测出发展为浸润癌的风险。

A team of scientists from the University of California San Francisco has identified distinct molecular markers that predict whether or not a woman is likely to develop subsequent invasive cancer after initial diagnosis with a noninvasive form of early breast cancer. The research, published by Cell Press in the November issue of Cancer Cell, provides critical information that can be used to determine whether a woman should receive more or less aggressive therapy.
旧金山的加利福尼亚大学的科学家小组已经发现了特殊的分子标志物，该标志物可以预测那些初次诊断为非浸润癌的早期乳癌的妇女是否可能会发展为继发性浸润癌。这个研究结果表发在《细胞》的第11期癌细胞版块里，该研究为决定是否一个女病人应该接受更多的或是较少的侵入性治疗提供了重要信息。

Approximately 12-15% of women diagnosed with ductal carcinoma in situ (DCIS), a tumor limited to milk ducts, develop a subsequent invasive cancer event within the first decade after surgical lumpectomy. However, due to the absence of reliable predictors to identify those women that will develop future tumors formation, all women diagnosed with DCIS tend to be offered similar treatment options. \"Identification of biomarkers that predict future tumor development would allow us to stratify a women's individual risk for subsequent invasive tumors and avoid over- and under- treatment,\" says lead author Dr. Thea D. Tlsty and clinician, Dr. Karla Kerlokowske, both from the Comprehensive Cancer Center at the University of California San Francisco.
即使在接受乳房肿瘤切除外科手术后的第一个十年内，仍有大约12-15%被诊断为原位管癌DICS的妇女（一种局限于输乳管的肿瘤）会发展为继发性的浸润性癌。然而，因为缺少可靠的预测这些妇女将来发展为浸润性癌的信息，所有诊断为DICS的妇女都将接受相似的治疗方案。“用生物标志物来预测肿瘤发展趋势的鉴定，允许我们根据不同个体发生继发性的浸润性癌风险进行分类，并且避免不适当的治疗。”文章第一作者 Thea D.Tlsty 博士和临床医生 Karla kerlowske如是说（两人都是来自旧金上的加利福尼亚大学的综合癌症中心）。

Dr. Tlsty, Gauthier and Berman hypothesized that cells capable of activating pathways linked to stress-induced cell death would not form subsequent tumors while cells that bypass stress signals would be more likely to eventually progress to tumor formation. The researchers evaluated molecular characteristics and their association with outcome in a group of women diagnosed with DCIS and found that expression of biomarkers indicative of a short-circuited response to cellular stress predicts DCIS with a worse outcome and is a defining characteristic of an aggressive phenotype called basal-like tumors. Conversely, a disease-free prognosis is associated with an intact response to cellular stress.
Tlsty,Gauthier和Berman博士提出这样假说：细胞的激活途径于压力诱导的细胞相关的将不会发展为继发性肿瘤；然而细胞的激活途径绕过压力信号的将更可能最终发展为肿瘤。研究者对分子特性及其对于一组被诊断为DCIS的妇女的关系进行了评估，研究表明：生物标志物显示出细胞压力反应较弱的预示着DICS的预后较差，这也是一种被称为基底样肿瘤的侵袭性表位的显著特征。相反，细胞压力反应完全于疾病的好的预后相关。

Mechanistic studies indicated that deregulation of the tumor suppressor Rb pathway is linked with the highly proliferative basal-like subtype of breast cancer and cancer recurrence. \"The combination of stress-activation and deregulation of p16/Rb signaling may represent a defining signature of basal-like carcinogenesis that can be assayed far in advance to the development of invasive disease and present clinical opportunities for appropriate aggressive intervention,\" concludes Dr. Tlsty.
机制研究表明：肿瘤抑制Rb通路的异常与高度扩散性的基底亚类型的乳癌和癌症复发有关。“压力激活和p16/Rb的异常可以代表基底癌的信号，而这些标志可以在进展为浸润癌之前就可一被诊断出来，以便于实施适当的临床干预。”Tlsty博士这样说。