Postoperative circulating tumor DNA combined with consensus molecular subtypes can better predict outcomes in stage III colon cancers: A prospective cohort study
Postoperative circulating tumor DNA combined with consensus molecular subtypes can better predict outcomes in stage III colon cancers: A prospective cohort study
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术后循环肿瘤 DNA 与共识分子亚型相结合可以更好地预测 III 期结肠癌的结果：一项前瞻性队列研究
DOI：
10.1016/j.ejca.2022.04.010
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发表时间：
2022-05-27
影响因子：
8.4
通讯作者：
Peng, Junjie
中科院分区：
文献类型：
--
作者：
Li, Yaqi;Mo, Shaobo;Peng, Junjie
背景：需要精确的风险分层方法来指导III期结肠癌的辅助化疗。在这里，我们将循环肿瘤DNA（ctDNA）与共识分子亚型（CMS）相结合，以改善III期结肠癌的风险分层。方法：我们对165例III期结肠癌患者进行了一项前瞻性、观察性队列研究。通过197个癌症相关基因的靶向测序组检测化疗前和化疗后收集的肿瘤组织和血浆中的体细胞变体。CMSs分类的特点是使用靶向RNA测序面板的788 genes.Results：我们分析了151化疗前和124化疗后的血浆，而130例患者的CMSs分类。ctDNA在15.9%的化疗前和8.9%的化疗后样品中可检测到。如果ctDNA在化疗前样本（风险比[HR]，3.585; P < 0.001）或化疗后样本（HR，3.337; P = 0.005）中可检测到，则无复发生存率（RFS）显著更差。在多变量分析中，化疗前ctDNA（HR，5.538; P < 0.001）和化疗后ctDNA状态（HR，3.272; P = 0.037）仍然与RFS独立相关。根据重新定义的复发风险分层，（CMS 4/T4或N2肿瘤ctDNA阴性）为5.3倍（HR，5.269; P = 0.025）比低风险患者更容易复发（CMS 1 -3/T3 N1肿瘤ctDNA阴性），而高危患者（ctDNA阳性）为14.6倍（HR，14.590; P < 0.001）更容易复发。术后ctDNA提示残留病变，结合CMS分级和反映肿瘤内在特征的临床风险，可以重新定义III期结肠癌的风险分层，并更好地预测复发。2022作者由Elsevier Ltd.发布。这是CC BY-NC许可下的开放获取文章（http：//creativecommons.org/licenses/by-nc/4.0/）。
Background: Precise methods for risk stratification to guide adjuvant chemo-therapy for stage III colon cancers are needed. Here, we combined circulating tumor DNA (ctDNA) with consensus molecular subtype (CMS) to improve risk stratification in stage III colon cancers. Methods: We conducted a prospective, observational cohort study of 165 patients with stage III colon cancers. Somatic variants in tumor tissues and plasmas collected pre-and post-chemo were detected via a targeted sequencing panel of 197 cancer-related genes. CMSs clas-sification was characterized using a targeted RNA sequencing panel of 788 genes.Results: We analyzed 151 pre-chemo and 124 post-chemo plasmas, while 130 patients were CMSs classified. ctDNA was detectable in 15.9% pre-chemo and 8.9% post-chemo samples. Significantly worse recurrence-free survival (RFS) was seen if ctDNA was detectable in prechemo samples (hazard ratio [HR], 3.585; P < 0.001) or in post-chemo samples (HR, 3.337; P = 0.005). Pre-chemo ctDNA (HR, 5.538; P < 0.001) and post-chemo ctDNA status (HR, 3.272; P = 0.037) remained independently associated with RFS in multivariate analysis. According to the redefined recurrence risk stratification, mid-risk patients (ctDNA-negative with CMS4/T4 or N2 tumors) were 5.3 times (HR, 5.269; P = 0.025) more likely to relapse than low-risk patients (ctDNA-negative with CMS1-3/T3N1 tumors), while high-risk patients (ctDNA-positive) were 14.6 times (HR, 14.590; P < 0.001) more likely to relapse.Conclusions: Postoperative ctDNA indicating residual disease, combined with CMSs classification and clinical risk reflecting the intrinsic characteristics of tumors, can redefine risk stratification of stage III colon cancers and better predict relapse. 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).