Background and Aims

The heterogeneity among colorectal tumors is probably due to differences in developmental pathways and might associate with patient survival times. We studied the relationship among markers of different subtypes of colorectal tumors and patient survival.

Methods

We pooled data from 7 observational studies, comprising 5010 patients with colorectal cancer. All the studies collected information on microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and mutations in KRAS and BRAF in tumors. Tumors with complete marker data were classified as type 1 (MSI-high, CIMP-positive, with pathogenic mutations in BRAF but not KRAS), type 2 (not MSI-high, CIMP-positive, with pathogenic mutations in BRAF but not KRAS), type 3 (not MSI-high or CIMP, with pathogenic mutations in KRAS but not BRAF), type 4 (not MSI-high or CIMP, no pathogenic mutations in BRAF or KRAS), or type 5 (MSI-high, no CIMP, no pathogenic mutations in BRAF or KRAS). We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for associations of these subtypes and tumor markers with disease-specific survival (DSS) and overall survival times, adjusting for age, sex, stage at diagnosis, and study population.

Results

Patients with type 2 colorectal tumors had significantly shorter time of DSS than patients with type 4 tumors (HR_DSS 1.66; 95% CI 1.33–2.07), regardless of sex, age, or stage at diagnosis. Patients without MSI-high tumors had significantly shorter time of DSS compared with patients with MSI-high tumors (HR_DSS 0.42; 95% CI 0.27–0.64), regardless of other tumor markers or stage, or patient sex or age.

Conclusions

In a pooled analysis of data from 7 observational studies of patients with colorectal cancer, we found that tumor subtypes, defined by combinations of 4 common tumor markers, were associated with differences in survival time. Colorectal tumor subtypes might therefore be used in determining patients’ prognoses.

中文翻译：

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结直肠肿瘤分子亚型与患者生存之间的关联，基于 7 项国际研究的汇总分析。

背景和目标

结直肠肿瘤之间的异质性可能是由于发育途径的差异，并可能与患者的生存时间有关。我们研究了结直肠肿瘤不同亚型的标志物与患者存活率之间的关系。

方法

我们汇总了 7 项观察性研究的数据，其中包括 5010 名结直肠癌患者。所有研究都收集了有关微卫星不稳定性 (MSI)、CpG 岛甲基化表型 (CIMP) 以及肿瘤中KRAS和BRAF突变的信息。具有完整标记数据的肿瘤被分类为 1 型（MSI 高，CIMP 阳性，BRAF有致病突变，但没有KRAS），2 型（MSI 高，CIMP 阳性，BRAF有致病突变，但没有KRAS 突变） , 3 型（不是 MSI-high 或 CIMP，在KRAS但不是BRAF 中有致病突变），4 型（不是 MSI-high 或 CIMP，在BRAF 中没有致病突变或KRAS），或 5 型（MSI 高，无 CIMP，BRAF或KRAS无致病突变）。我们使用 Cox 回归来估计这些亚型和肿瘤标志物与疾病特异性生存率 (DSS) 和总生存时间的关联的风险比 (HR) 和 95% 置信区间 (CI)，并针对年龄、性别、诊断阶段、和研究人口。

结果

2 型结直肠肿瘤患者的 DSS 时间明显短于 4 型肿瘤患者（HR _DSS 1.66；95% CI 1.33–2.07），无论性别、年龄或诊断分期如何。与 MSI 高肿瘤患者相比，无 MSI 高肿瘤患者的 DSS 时间显着缩短（HR _DSS 0.42；95% CI 0.27–0.64），无论其他肿瘤标志物或分期，或患者性别或年龄。

结论

在对 7 项结直肠癌患者观察性研究数据的汇总分析中，我们发现由 4 种常见肿瘤标志物组合定义的肿瘤亚型与生存时间的差异相关。因此，结直肠肿瘤亚型可用于确定患者的预后。