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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Molecular serum portraits in patients with primary breast cancer predict the development of distant metastases
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Molecular serum portraits in patients with primary breast cancer predict the development of distant metastases

机译：原发性乳腺癌患者的分子血清肖像可预测远处转移的发生

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摘要

The risk of distant recurrence in breast cancer patients is difficult to assess with current clinical and histopathological parameters, and no validated serum biomarkers currently exist. Using a recently developed recombinant antibody microarray platform containing 135 antibodies against 65 mainly immunoregulatory proteins, we screened 240 sera from 64 patients with primary breast cancer. This unique longitudinal sample material was collected from each patient between 0 and 36 mo after the primary operation. The velocity for each serum protein was determined by comparing the samples collected at the primary operation and then 3-6 mo later. A 21-protein signature was identified, using leave-one-out cross-validation together with a backward elimination strategy in a training cohort. This signature was tested and evaluated subsequently in an independent test cohort (prevalidation). The risk of developing distant recurrence after primary operation could be assessed for each patient, using her molecular portraits. The results from this prevalidation study showed that patients could be classified into high-versus low-risk groups for developing metastatic breast cancer with a receiver operating characteristic area under the curve of 0.85. This risk assessment was not dependent on the type of adjuvant therapy received by the patients. Even more importantly, we demonstrated that this protein signature provided an added value compared with conventional clinical parameters. Consequently, we present here a candidate serum biomarker signature able to classify patients with primary breast cancer according to their risk of developing distant recurrence, with an accuracy outperforming current procedures.
机译：用当前的临床和组织病理学参数很难评估乳腺癌患者远处复发的风险，并且目前不存在经过验证的血清生物标志物。使用最近开发的重组抗体微阵列平台，该平台包含针对65种主要免疫调节蛋白的135种抗体，我们从64例原发性乳腺癌患者中筛选了240份血清。初次手术后，在0至36个月之间从每位患者收集这种独特的纵向样品材料。通过比较在初次操作时收集的样品，然后在3-6 mo后比较，来确定每种血清蛋白的速度。在训练队列中使用留一法交叉验证和后向消除策略，鉴定出21种蛋白质的特征。随后在独立的测试队列中对该签名进行了测试和评估（预验证）。可以通过每个患者的分子画像评估初次手术后发生远处复发的风险。这项预先验证研究的结果表明，可以将患转移性乳腺癌的患者分为高风险组和低风险组，接受者的手术特征区域在0.85曲线以下。该风险评估不取决于患者接受的辅助治疗的类型。更重要的是，我们证明了与常规临床参数相比，这种蛋白质特征提供了附加价值。因此，我们在这里提出了一种候选血清生物标志物签名，能够根据原发性乳腺癌患者远距离复发的风险对其进行分类，其准确性优于目前的程序。

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    Anders Carlsson; Christer Wingren; Malin Kristensson; Carsten Rose; Marten Fernoe; Hakan Olsson; Helena Jernstrom; Sara Ek; Elin Gustavsson; Christian Ingvar; Mattias Ohlsson; Carsten Peterson; Carl A. K. Borrebaeck;

  • 作者单位

    Department of Immunotechnology, Lund University, BMC D13, SE-22184 Lund, Sweden,CREATE Health, Lund University, BMC D13, SE-22184 Lund, Sweden;

    Department of Immunotechnology, Lund University, BMC D13, SE-22184 Lund, Sweden,CREATE Health, Lund University, BMC D13, SE-22184 Lund, Sweden;

    Department of Immunotechnology, Lund University, BMC D13, SE-22184 Lund, Sweden,CREATE Health, Lund University, BMC D13, SE-22184 Lund, Sweden;

    CREATE Health, Lund University, BMC D13, SE-22184 Lund, Sweden,Department of Oncology, Lund University Hospital, SE-221 85 Lund, Sweden;

    Department of Oncology, Lund University Hospital, SE-221 85 Lund, Sweden;

    Department of Oncology, Lund University Hospital, SE-221 85 Lund, Sweden;

    Department of Oncology, Lund University Hospital, SE-221 85 Lund, Sweden;

    Department of Immunotechnology, Lund University, BMC D13, SE-22184 Lund, Sweden,CREATE Health, Lund University, BMC D13, SE-22184 Lund, Sweden;

    Department of Immunotechnology, Lund University, BMC D13, SE-22184 Lund, Sweden,CREATE Health, Lund University, BMC D13, SE-22184 Lund, Sweden;

    Department of Surgery,Lund University, BMC D13, SE-22184 Lund, Sweden;

    CREATE Health, Lund University, BMC D13, SE-22184 Lund, Sweden,Division of Computational Biology, Lund University, BMC D13, SE-22184 Lund, Sweden;

    CREATE Health, Lund University, BMC D13, SE-22184 Lund, Sweden,Division of Computational Biology, Lund University, BMC D13, SE-22184 Lund, Sweden;

    Department of Immunotechnology, Lund University, BMC D13, SE-22184 Lund, Sweden,CREATE Health, Lund University, BMC D13, SE-22184 Lund, Sweden;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    affinity proteomics; monitoring disease; prognosis; tumour relaps; malignancy;

    机译：亲和蛋白质组学监测疾病;预后肿瘤复发恶性肿瘤;

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