Serum IL-8 level as a candidate prognostic marker of response to anti-angiogenic therapy for metastatic colorectal cancer
Serum IL-8 level as a candidate prognostic marker of response to anti-angiogenic therapy for metastatic colorectal cancer
复制标题
血清 IL-8 水平作为转移性结直肠癌抗血管生成治疗反应的候选预后标志物
DOI：
10.1007/s00384-020-03748-y
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发表时间：
2020
影响因子：
2.8
通讯作者：
Yamaguchi Kensei
中科院分区：
文献类型：
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作者：
Suenaga Mitsukuni;Mashima Tetsuo;Kawata Naomi;Wakatsuki Takeru;Dan Shingo;Seimiya Hiroyuki;Yamaguchi Kensei
目的转移性结直肠癌（mCRC）患者肝脏转移（LM）与预后不良相关。在这里，我们研究了在一线（FL）或一线（SL）环境中接受抗血管生成药物治疗的伴有或不伴有LM的mCRC患者的几种血清因子的预后效用。方法采用单研究所合并分析，对125例患者进行联合队列分析：FL队列接受贝伐单抗治疗（71例），SL队列接受瑞非尼治疗（54例）。在基线（BL）和治疗期间采集血样，用ELISA法测定血清因子。采用Kaplan-Meier曲线、log-rank检验和Cox比例风险回归分析总生存期（OS）。结果在联合队列的单因素分析中，右侧结直肠癌、原发未切除肿瘤、野生型kras、LM、≥2个转移位点和SL与较短的生存期相关；在多变量分析中，LM和SL仍然显著。BL患者血清血管生成素-2 （ang2）水平≥2190.3 pg/ml，白细胞介素(IL)-8水平≥15.1 pg/ml与LM显著相关。使用这些临界值，在BL时，Ang-2或IL-8水平较高的患者比BL水平较低的患者有更短的OS （Ang-2：风险比[HR] 2.57, 95%可信区间[CI] 1.47-4.51，P= 0.001; IL-8: HR 4.31, 95%CI 2.11-8.79，P< 0.001）。在多变量分析中，高血清IL-8水平仍然是较短生存期的显著预测因子（HR 3.24, 95%CI 1.47-7.16，P= 0.004）。结论mCRC患者外周血IL-8和Ang-2水平与LM相关。无论治疗时间如何，IL-8可能是抗血管生成治疗反应的预后标志物。
PurposeLiver metastasis (LM) is associated with poor prognosis in patients with metastatic colorectal cancer (mCRC). Here, we investigated the prognostic utility of several serum factors in mCRC patients with or without LM who were treated with anti-angiogenic agents in first-line (FL) or salvage-line (SL) settings.MethodsA combined cohort of 125 patients was analyzed in this single institute pooled analysis: FL cohort receiving bevacizumab (n= 71) and SL cohort receiving regorafenib (n= 54). Blood samples were obtained at baseline (BL) and during treatment, and serum factors were measured by ELISA. Overall survival (OS) was analyzed using Kaplan–Meier curves, the log-rank test, and Cox proportional hazard regression methods.ResultsIn univariate analysis of the combined cohort, right-sided CRC, primary unresected tumor, wild-typeKRAS, LM, ≥ 2 metastatic sites, and SL were associated with shorter OS; in multivariable analysis, LM and SL remained significant. Serum angiopoietin-2 (Ang-2) levels ≥ 2190.3 pg/ml and interleukin (IL)-8 levels ≥ 15.1 pg/ml at BL were significantly associated with LM. Using these cut-off values, patients with higher Ang-2 or IL-8 levels at BL had shorter OS than those with lower BL levels (Ang-2: hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.47–4.51,P= 0.001; IL-8: HR 4.31, 95%CI 2.11–8.79,P< 0.001). High serum IL-8 level remained a significant predictor of shorter OS in multivariable analysis (HR 3.24, 95%CI 1.47–7.16,P= 0.004).ConclusionCirculating IL-8 and Ang-2 levels are associated with LM in mCRC patients. IL-8 may be a prognostic marker of response to anti-angiogenic therapy, regardless of the treatment timing.