Abstract：
BACKGROUND: The consensus molecular subtypes (CMSs) of colorectal cancer (CRC) capture tumor heterogeneity at the gene-expression level. Currently, a restricted number of molecular features are used to guide treatment for CRC. We summarize the evidence on the clinical value of the CMSs.
METHODS: We systematically identified studies in Medline and Embase that evaluated the prognostic and predictive value of CMSs in CRC patients. A random-effect meta-analysis was performed on prognostic data. Predictive data were summarized.
RESULTS: In local disease, CMS4 tumors were associated with worse overall survival (OS) compared to CMS1 (hazard ratio [HR] = 3.28, 95% confidence interval = 1.27 to 8.47) and CMS2 cancers (HR = 2.60, 95% confidence interval= 1.93 to 3.50). In metastatic disease, CMS1 consistently had worse survival than CMS2-4 (OS HR range = 0.33 to 0.55; progression-free survival HR range = 0.53 to 0.89). Adjuvant chemotherapy in stage II and III CRC was most beneficial for OS in CMS2 and CMS3 (HR range = 0.16 to 0.45) and not effective in CMS4 tumors. In metastatic CMS4 cancers, an irinotecan-based regimen improved outcome as compared to oxaliplatin (HR range = 0.31 to 0.72). The addition of bevacizumab seemed beneficial in CMS1, and anti-EGFR therapy improved outcome for KRAS wildtype CMS2 patients.
CONCLUSIONS: The CMS classification holds clear potential for clinical use in predicting both prognosis and response to systemic therapy, which seems to be independent of the classifier used. Prospective studies are warranted to support implementation of the CMS taxonomy in clinical practice.
METHODS: We systematically identified studies in Medline and Embase that evaluated the prognostic and predictive value of CMSs in CRC patients. A random-effect meta-analysis was performed on prognostic data. Predictive data were summarized.
RESULTS: In local disease, CMS4 tumors were associated with worse overall survival (OS) compared to CMS1 (hazard ratio [HR] = 3.28, 95% confidence interval = 1.27 to 8.47) and CMS2 cancers (HR = 2.60, 95% confidence interval= 1.93 to 3.50). In metastatic disease, CMS1 consistently had worse survival than CMS2-4 (OS HR range = 0.33 to 0.55; progression-free survival HR range = 0.53 to 0.89). Adjuvant chemotherapy in stage II and III CRC was most beneficial for OS in CMS2 and CMS3 (HR range = 0.16 to 0.45) and not effective in CMS4 tumors. In metastatic CMS4 cancers, an irinotecan-based regimen improved outcome as compared to oxaliplatin (HR range = 0.31 to 0.72). The addition of bevacizumab seemed beneficial in CMS1, and anti-EGFR therapy improved outcome for KRAS wildtype CMS2 patients.
CONCLUSIONS: The CMS classification holds clear potential for clinical use in predicting both prognosis and response to systemic therapy, which seems to be independent of the classifier used. Prospective studies are warranted to support implementation of the CMS taxonomy in clinical practice.
摘要：
背景：结直肠癌（CRC）的共有分子亚型（CMSs）在基因表达水平上捕获了肿瘤异质性。目前,有限数量的分子特征用于指导CRC的治疗.我们总结了CMSs临床价值的证据。
方法：我们系统地确定了Medline和Embase的研究，这些研究评估了CMSs在CRC患者中的预后和预测价值。对预后数据进行随机效应荟萃分析。对预测数据进行了总结。
结果：在局部疾病中，与CMS1（风险比[HR]=3.28，95％置信区间=1.27至8.47）和CMS2癌症（HR=2.60，95％置信区间=1.93至3.50）相比，CMS4肿瘤与更差的总生存期（OS）相关。在转移性疾病中，CMS1的生存率始终比CMS2-4差（OSHR范围=0.33至0.55；无进展生存期HR范围=0.53至0.89）。II期和III期CRC中的辅助化疗对CMS2和CMS3中的OS最有利(HR范围=0.16至0.45),而对CMS4肿瘤无效。在转移性CMS4癌症中，与奥沙利铂相比,基于伊立替康的方案改善了结局(HR范围=0.31~0.72).贝伐单抗的加入似乎对CMS1有益，抗EGFR治疗改善了KRAS野生型CMS2患者的预后。
结论：CMS分类在预测预后和对全身治疗的反应方面具有明确的临床应用潜力。这似乎是独立于使用的分类器。有必要进行前瞻性研究，以支持在临床实践中实施CMS分类法。
方法：我们系统地确定了Medline和Embase的研究，这些研究评估了CMSs在CRC患者中的预后和预测价值。对预后数据进行随机效应荟萃分析。对预测数据进行了总结。
结果：在局部疾病中，与CMS1（风险比[HR]=3.28，95％置信区间=1.27至8.47）和CMS2癌症（HR=2.60，95％置信区间=1.93至3.50）相比，CMS4肿瘤与更差的总生存期（OS）相关。在转移性疾病中，CMS1的生存率始终比CMS2-4差（OSHR范围=0.33至0.55；无进展生存期HR范围=0.53至0.89）。II期和III期CRC中的辅助化疗对CMS2和CMS3中的OS最有利(HR范围=0.16至0.45),而对CMS4肿瘤无效。在转移性CMS4癌症中，与奥沙利铂相比,基于伊立替康的方案改善了结局(HR范围=0.31~0.72).贝伐单抗的加入似乎对CMS1有益，抗EGFR治疗改善了KRAS野生型CMS2患者的预后。
结论：CMS分类在预测预后和对全身治疗的反应方面具有明确的临床应用潜力。这似乎是独立于使用的分类器。有必要进行前瞻性研究，以支持在临床实践中实施CMS分类法。
