Zhang Ben Y, Jones Jeremy C, Briggler Andrew M, Hubbard Joleen M, Kipp Benjamin R, Sargent Daniel J, Dixon Jesse G, Grothey Axel
Department of Oncology, Mayo Clinic, Rochester, MN.
Department of Medicine, Mayo Clinic, Rochester, MN.
Clin Colorectal Cancer. 2017 Jun;16(2):124-128. doi: 10.1016/j.clcc.2016.09.003. Epub 2016 Sep 17.
Although the lack of CDX2 expression has recently been proposed as a potential biomarker for a high risk of relapse in patients with stage II and III colon cancer after complete surgical resection, its prognostic role in metastatic colorectal cancer (CRC) remains unclear and warrants investigation.
We identified 145 patients treated at our institution from 2006 to 2016, including 66 patients with CDX2-negative metastatic CRC and a comparison cohort of 79 patients with CDX2-positive metastatic CRC. Overall survival (OS) and progression-free survival (PFS) for first-line systemic therapy were estimated using the Kaplan-Meier method. The associations of CDX2 expression with survival were evaluated using Cox proportional hazards regression models.
The prevalence of absent CDX2 expression in our cohort was 5.6%. Patients with CDX2-negative metastatic CRC were significantly more likely to be female, and to have right-sided primary tumors, poorly differentiated histologic features, and distant lymph node metastasis. The median OS for patients with CDX2-negative and -positive metastatic CRC was 8 and 39 months, respectively (hazard ratio [HR], 4.04; 95% confidence interval [CI], 2.49-6.54; P < .0001). After adjusting for covariates in a multivariate model, the association of a lack of CDX2 expression and OS remained statistically significant (HR, 4.52; 95% CI, 2.50-8.17; P < .0001). In addition, the median PFS (3 vs. 10 months; HR, 2.23; 95% CI, 1.52-3.27; P < .0001) for first-line chemotherapy was significantly decreased in patients with CDX2-negative metastatic CRC.
The results of the present study show that a lack of CDX2 expression in metastatic CRC is an adverse prognostic feature and a potential negative predictor of the response to chemotherapy.
尽管最近有人提出缺乏CDX2表达可作为II期和III期结肠癌患者完全手术切除后高复发风险的潜在生物标志物，但其在转移性结直肠癌（CRC）中的预后作用仍不清楚，值得研究。
我们确定了2006年至2016年在我院接受治疗的145例患者，其中包括66例CDX2阴性转移性CRC患者和79例CDX2阳性转移性CRC患者的对照队列。采用Kaplan-Meier法估计一线全身治疗的总生存期（OS）和无进展生存期（PFS）。使用Cox比例风险回归模型评估CDX2表达与生存期的关联。
我们队列中CDX2表达缺失的患病率为5.6%。CDX2阴性转移性CRC患者更可能为女性，且有右侧原发性肿瘤、低分化组织学特征和远处淋巴结转移。CDX2阴性和阳性转移性CRC患者的中位OS分别为8个月和39个月（风险比[HR]，4.04；95%置信区间[CI]，2.49-6.54；P < .0001）。在多变量模型中对协变量进行调整后，CDX2表达缺失与OS之间的关联仍具有统计学意义（HR，4.52；95%CI，2.50-8.17；P < .0001）。此外，CDX2阴性转移性CRC患者一线化疗的中位PFS（3个月对10个月；HR，2.23；95%CI，1.52-3.27；P < .0001）显著降低。
本研究结果表明，转移性CRC中CDX2表达缺失是不良预后特征，也是化疗反应的潜在阴性预测指标。
