Prognostic value of baseline seric Syndecan-1 in initially unresectable metastatic colorectal cancer patients: a simple biological score
Prognostic value of baseline seric Syndecan-1 in initially unresectable metastatic colorectal cancer patients: a simple biological score
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DOI：
10.1002/ijc.30367
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发表时间：
2016-11-15
影响因子：
6.4
通讯作者：
Vernerey, Dewi
中科院分区：
文献类型：
--
作者：
Jary, Marine;Lecomte, Thierry;Vernerey, Dewi
在一线转移性结直肠癌 (mCRC) 中，缺乏允许死亡风险和治疗策略分层的基线预后因素。 Syndecan-1 (CD138) 可溶形式从未被描述为 mCRC 的预后生物标志物。我们研究了其对总生存期 (OS) 的额外预后价值。在两项独立的前瞻性临床试验中，诊断时患有不可切除疾病的 mCRC 患者接受基于贝伐单抗的化疗（开发组：n=126，验证组：n=51，分别为研究 NCT00489697 和研究 NCT00544011）。在基线时收集血清用于 CD138 测量。评估了 OS 决定因素，并根据最终的多变量模型提出了预后评分。确定了两个独立的 OS 预后因素：乳酸脱氢酶 (LDH) 高水平 (p=0.0066) 和 log-CD138 高水平 (p=0.0190)。 CD138 二元信息（截止值：75 ng/mL）的确定允许使用 CD138 和 LDH 值评估生物预后评分，确定三个死亡风险组（低、中和高风险组的中位 OS 分别 = 38.9、30.1 和 19.8 个月；p < 0.0001）。该分数具有良好的判别能力（C-index=0.63）。这些结果在验证集中得到了外部确认。我们的研究提供了强有力的证据，支持可溶性 CD138 的额外基线对 mCRC 患者的 OS 预后价值。提出了一个简单的生物评分系统，包括 LDH 和 CD138 二进制状态值。
In first-line metastatic colorectal cancer (mCRC), baseline prognostic factors allowing death risk and treatment strategy stratification are lacking. Syndecan-1 (CD138) soluble form was never described as a prognostic biomarker in mCRC. We investigated its additional prognostic value for overall survival (OS). mCRC patients with unresectable disease at diagnosis were treated with bevacizumab-based chemotherapy in two independent prospective clinical trials (development set: n=126, validation set: n=51, study NCT00489697 and study NCT00544011, respectively). Serums were collected at baseline for CD138 measurement. OS determinants were assessed and, based on the final multivariate model, a prognostic score was proposed. Two independent OS prognostic factors were identified: Lactate Dehydrogenase (LDH) high level (p=0.0066) and log-CD138 high level (p=0.0190). The determination of CD138 binary information (cutoff: 75 ng/mL) allowed the assessment of a biological prognostic score with CD138 and LDH values, identifying three risk groups for death (median OS= 38.9, 30.1 and 19.8 months for the low, intermediate and high risk groups, respectively; p < 0.0001). This score had a good discrimination ability (C-index=0.63). These results were externally confirmed in the validation set. Our study provides robust evidence in favor of the additional baseline soluble CD138 prognostic value for OS, in mCRC patients. A simple biological scoring system is proposed including LDH and CD138 binary status values.