A chemokine/chemokine receptor signature potentially predicts clinical outcome in colorectal cancer patients.
A chemokine/chemokine receptor signature potentially predicts clinical outcome in colorectal cancer patients.
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DOI：
10.3233/cbm-190210
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发表时间：
2019
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影响因子：
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通讯作者：
Lokeshwar VB
中科院分区：
文献类型：
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作者：
Mitchell A;Hasanali SL;Morera DS;Baskar R;Wang X;Khan R;Talukder A;Li CS;Manoharan M;Jordan AR;Wang J;Bollag RJ;Singh N;Albo D;Ghosh S;Lokeshwar VB
结直肠癌（CRC）中趋化因子/趋化因子受体的差异表达可以使患者肿瘤的分子表征用于预测临床结果。评估这些分子在CRC队列和CRC TCGA数据集中的预后能力。通过RT-qPCR分析了76例CRC标本（正常：27例，肿瘤：49例;临床队列）中的趋化因子（CXCL-12 α、CXCL-12β、IL-17 A、CXCL-8、GM-CSF）和趋化因子受体（CXCR-4、CXCR-7）转录本。从TCGA数据集（n=375）分析RNA-Seq数据。转录水平与结果相关;分析：单变量，多变量，Kaplan-Meier。在临床队列中，CRC标本中趋化因子/趋化因子受体水平升高3-10倍（P≤0.004），发生转移的患者中更高（P=0.03-<0.0001）。CXCR-4、CXCR-7、CXCL-12α、CXCL-8、IL-17和GM-CSF水平预测转移（P≤0.0421）和/或总生存期（OS; P≤0.0373）。CXCR-4+CXCR-7+CXCL-12标记物（CXCR-4/7+CXCL-12（α/β）特征）将患者分层为转移风险（P=0.0014; OR，2.72）和OS（P=0.0442; OR，2.7）;敏感性：86.67%，特异性：97.06%。在TCGA数据集中，CXCR-4/7+CXCL-12特征预测转移（P=0.011; OR，2.72）和OS（P=0.0006; OR：4.04）。在这两个数据集中，签名是临床结果的独立预测因子。来自两个队列的451份标本的结果显示，CXCR-4/7+CXCL-12特征可能预测CRC患者的结局，并可能允许早期干预。
Differential expression of chemokines/chemokine receptors in colorectal cancer (CRC) may enable molecular characterization of patients’ tumors for predicting clinical outcome. To evaluate the prognostic ability of these molecules in a CRC cohort and the CRC TCGA-dataset. Chemokine (CXCL-12α, CXCL-12β, IL-17A, CXCL-8, GM-CSF) and chemokine receptor (CXCR-4, CXCR-7) transcripts were analyzed by RT-qPCR in 76 CRC specimens (normal: 27, tumor: 49; clinical cohort). RNA-Seq data was analyzed from the TCGA-dataset (n=375). Transcript levels were correlated with outcome; analyses: univariate, multivariable, Kaplan-Meier. In the clinical cohort, chemokine/chemokine receptor levels were elevated 3–10-fold in CRC specimens (P≤0.004) and were higher in patients who developed metastasis (P=0.03-<0.0001). CXCR-4, CXCR-7, CXCL-12α, CXCL-8, IL-17 and GM-CSF levels predicted metastasis (P≤0.0421) and/or overall survival (OS; P≤0.0373). The CXCR-4+CXCR-7+CXCL-12 marker (CXCR-4/7+CXCL-12(α/β) signature) stratified patients into risk for metastasis (P=0.0014; OR, 2.72) and OS (P=0.0442; OR, 2.7); sensitivity: 86.67%, specificity: 97.06%. In the TCGA-dataset, the CXCR-4/7+CXCL-12 signature predicted metastasis (P=0.011; OR, 2.72) and OS (P=0.0006; OR: 4.04). In both datasets, the signature was an independent predictor of clinical outcome. Results of 451 specimens from both cohorts reveal that the CXCR-4/7+CXCL-12 signature potentially predicts outcome in CRC patients and may allow earlier intervention.