Still proliferating CD44+/Ki67+ tumor cells after neoadjuvant radiochemotherapy identify rectal cancer patients with poor survival
Still proliferating CD44+/Ki67+ tumor cells after neoadjuvant radiochemotherapy identify rectal cancer patients with poor survival
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DOI：
10.1016/j.ejso.2021.03.250
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发表时间：
2021-07-14
期刊：
影响因子：
3.8
通讯作者：
Tarantino, Ignazio
中科院分区：
文献类型：
--
作者：
Klose, Johannes;Schmitt, Annelene;Tarantino, Ignazio
简介：三分之一接受根治性治疗的直肠癌患者会出现远处复发，尤其是肝转移，这仍然是一个尚未解决的问题。识别高危患者对于实现个体化治疗至关重要。材料和方法：纳入2001年1月至2015年12月期间新辅助放化疗后因组织学证实的直肠癌接受根治性切除的所有患者。对切片进行 Ki67、CD44、细胞凋亡和 CD133 染色。根据是否发现有（CD44（+）/Ki67（+））或没有（CD44（+）/Ki67（+））仍在增殖的肿瘤细胞对患者进行分类。结果：选择了218名接受R0切除的I-III期直肠癌患者。在这些患者中，有 37 名（17%）发现了 CD44(+)/Ki67(+) 肿瘤细胞。在多变量Cox回归分析中，CD44+/Ki67+细胞患者的总体生存率（HR：3.84，95% CI：1.77-8.31，p = 0.001）和相对生存率（HR 3.44，95% CI：1.46-8.09）显着受损。之前的结果在倾向得分匹配后得到了证实。在中介分析中，CD44(+)/Ki67(+)细胞的存在与总体生存率(HR 1.92，95% CI：1.09-9.28)和相对生存率(HR 1.63，95% CI：1.31-6.38)的显着直接影响相关。结论：术后仍存在增殖的CD44(+)/Ki67(+)肿瘤细胞新辅助放化疗与肿瘤长期结局受损相关。应对这些细胞进行表征。 (C) 2021 Elsevier Ltd、BASO（类似于癌症手术协会）和欧洲肿瘤外科学会。版权所有。
Introduction: Distant recurrence, especially liver metastases, occurs in one-third of rectal cancer patients initially treated with curative therapy and is still an unsolved problem. The identification of patients at risk is crucial for enabling individualized treatment.Material and methods: All patients undergoing curative resection for histologically confirmed rectal cancer after neoadjuvant radiochemotherapy between January 2001 and December 2015 were included. Sections were stained for Ki67, CD44, apoptosis and CD133. Patients were categorized based on whether they were found to have (CD44(+)/Ki67(+)) or not have (CD44(+)/Ki67(+)) still proliferating tumor cells.Results: 218 patients who underwent R0 resection for stage I-III rectal cancer were selected. In 37 ( 17%) of these patients, CD44(+)/Ki67(+) tumor cells were found. In multivariable Cox regression analysis, patients with CD44(+)/Ki67(+) cells had significantly impaired overall (hazard ratio (HR): 3.84, 95% CI: 1.77-8.31, p = 0.001) and relative survival (HR 3.44, 95% CI: 1.46-8.09). The previous results were confirmed after propensity-score matching. In mediation-analysis, the presence of CD44(+)/Ki67(+) cells was associated with a substantial direct effect on overall (HR 1.92, 95% CI: 1.09-9.28) and relative survival (HR 1.63, 95% CI: 1.31-6.38).Conclusions: The presence of still proliferating CD44(+)/Ki67(+) tumor cells after neoadjuvant radiochemotherapy was associated with impaired oncological long-term outcomes. Characterization of these cells should be performed. (C) 2021 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.