野生型 APC 与转移性微卫星稳定结直肠癌患者的不良预后相关。

Wild-type APC Is Associated with Poor Survival in Metastatic Microsatellite Stable Colorectal Cancer.

机构信息

Department of Medical Oncology and Therapeutics Research, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, California, USA.

Center for Informatics, Department of Computational and Quantitative Medicine, City of Hope National Medical Center, Duarte, California, USA.

出版信息

Oncologist. 2021 Mar;26(3):208-214. doi: 10.1002/onco.13607. Epub 2020 Dec 7.

DOI:10.1002/onco.13607

PMID:33230914

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7930429/

Abstract

BACKGROUND

The prognostic implication of wild-type APC (APC-WT) in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) is not well defined.

MATERIALS AND METHODS

APC prognostic value was evaluated retrospectively in two independent cohorts of patient with MSS mCRC with a confirmatory analysis from a public data set from Memorial Sloan Kettering Cancer Center (MSKCC).

RESULTS

In comparison with the APC-mutant (APC-MT) population (n = 255), APC-WT patients (n = 86) tended to be younger (59% of age < 40 vs. 26% of age > 50), right-sided (41.7% vs. 27%), BRAF mutated (23.3% vs. 0.8%), and KRAS wild type (65.1% vs. 49.8%). Alternative WNT pathway alterations, RNF43 and CTNNB1, were over-represented in the APC-WT versus APC-MT population (7% vs. 0.4% and 4.7% vs. 0.4%, respectively). APC-WT patients had a worse overall survival (OS) than APC-MT patients (22.6 vs. 45.6 months, p < .0001). Using a multivariate model correcting for primary tumor location, RAS and BRAF status, APC-WT was predictive of poor survival (APC-MT vs. APC-WT, hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.44-0.86, p = .0037). The prognostic implication of APC-WT on OS was confirmed further in a similar multivariate model of 934 stage IV patients from MSKCC public database (APC-MT vs. APC-WT, HR, 0.63, 95% CI, 0.49-0.81, p < .0001).

CONCLUSION

APC-WT is associated with poor OS in MSS mCRC regardless of RAS and BRAF status. Compared with APC-MT mCRC tumors, APC-WT tumors were associated with other Wnt activating alterations, including RNF43 and CTNBB1. Our data suggest alternative therapy needs to be investigated in APC-WT patients.

IMPLICATIONS FOR PRACTICE

Patients with microsatellite stable metastatic colorectal cancer with wild-type APC had a worse overall survival than patients with mutated APC regardless of RAS/RAF status. APC status should be considered as a stratification factor in prospective trials, and novel therapeutic strategies need to be developed for this subgroup of patients.

摘要

背景

微卫星稳定（MSS）转移性结直肠癌（mCRC）中野生型 APC（APC-WT）的预后意义尚不清楚。

材料和方法

我们回顾性地评估了来自 Memorial Sloan Kettering Cancer Center（MSKCC）公共数据集的两个独立 MSS mCRC 患者队列中 APC 的预后价值，并进行了确认性分析。

结果

与 APC 突变（APC-MT）人群（n=255）相比，APC-WT 患者（n=86）更年轻（<40 岁者占 59%，>50 岁者占 26%），右侧（41.7% vs. 27%），BRAF 突变（23.3% vs. 0.8%），KRAS 野生型（65.1% vs. 49.8%）。与 APC-MT 相比，APC-WT 人群中存在更多的替代 WNT 通路改变，RNF43 和 CTNNB1（分别为 7% vs. 0.4%和 4.7% vs. 0.4%）。APC-WT 患者的总生存（OS）比 APC-MT 患者差（22.6 个月 vs. 45.6 个月，p<0.0001）。在对原发肿瘤位置、RAS 和 BRAF 状态进行多变量模型校正后，APC-WT 预测生存不良（APC-MT 与 APC-WT，风险比 [HR]，0.62；95%置信区间 [CI]，0.44-0.86，p=0.0037）。在来自 MSKCC 公共数据库的 934 例 IV 期患者的类似多变量模型中，进一步证实了 APC-WT 对 OS 的预后意义（APC-MT 与 APC-WT，HR，0.63，95%CI，0.49-0.81，p<0.0001）。