Soluble programmed death-ligand 1 (sPDL1) and neutrophil-to-lymphocyte ratio (NLR) predicts survival in advanced biliary tract cancer patients treated with palliative chemotherapy.
Soluble programmed death-ligand 1 (sPDL1) and neutrophil-to-lymphocyte ratio (NLR) predicts survival in advanced biliary tract cancer patients treated with palliative chemotherapy.
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DOI：
10.18632/oncotarget.12810
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发表时间：
2016-11-22
期刊：
影响因子：
--
通讯作者：
Oh DY
中科院分区：
文献类型：
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作者：
Ha H;Nam AR;Bang JH;Park JE;Kim TY;Lee KH;Han SW;Im SA;Kim TY;Bang YJ;Oh DY
程序性死亡配体1（PD-L1）在肿瘤组织中的表达作为免疫肿瘤学研究的候选生物标志物正在研究中。PD-L1的可溶形式（sPDL 1）被认为具有免疫抑制活性。在这项研究中，我们检测了血清中sPDL 1的水平，并评估其在胆道癌（BTC）的预后意义。158例中晚期胆管癌患者（肝内胆管癌68例，胆囊癌56例，肝外胆管癌22例，壶腹癌12例）在姑息化疗前采血。采用酶联免疫吸附试验测定血清sPDL 1。临床资料包括中性粒细胞/淋巴细胞比值（NLR）、血小板/淋巴细胞比值（PLR）和全身免疫炎症指数（SII，中性粒细胞×血小板/淋巴细胞）。使用简单的随机抽样方法将患者分配到两个队列（训练和验证队列），以验证每个标志物的截止值。使用双重交叉验证方法进行验证。所有患者的总生存期（OS）为9.07个月（95%CI：8.20-11.33）。中位sPDL 1为1.20 ng/mL（范围0.03-7.28，平均值1.50，SD 1.22）。中位NLR、PLR和SII分别为2.60、142.85和584.93。高sPDL 1（≥0.94 ng/mL）患者的OS比低sPDL 1患者差（7.93 vs. 14.10个月，HR 1.891（1.35-2.65），p<0.001）。多因素分析显示，sPDL 1和NLR增高是独立的不良预后因素。结论：血清sPDL 1水平可作为判断姑息性化疗晚期BTC患者预后的指标。
Programmed death-ligand 1 (PD-L1) expression in tumor tissue is under investigation as a candidate biomarker in immuno-oncology dug development. The soluble form of PD-L1 (sPDL1) is suggested to have immunosuppressive activity. In this study, we measured the serum level of sPDL1 and evaluated its prognostic implication in biliary tract cancer (BTC). Blood was collected from 158 advanced BTC patients (68 intrahepatic cholangiocarcinoma, 56 gallbladder cancer, 22 extrahepatic cholangiocarcinoma and 12 ampulla of vater cancer) before initiation of palliative chemotherapy. Serum sPDL1 was measured using an enzyme-linked immunosorbent assay. Clinical data included neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII, neutrophil × platelet/lymphocyte). The patients were assigned to two cohorts (training and validation cohort) using a simple random sampling method to validate the cut-off value of each marker. Validation was performed using a twofold cross-validation method. Overall survival (OS) of all patients was 9.07 months (95% CI: 8.20-11.33). Median sPDL1 was 1.20 ng/mL (range 0.03-7.28, mean 1.50, SD 1.22). Median NLR, PLR and SII were 2.60, 142.85 and 584.93, respectively. Patients with high sPDL1 (≥0.94 ng/mL) showed worse OS than patients with low sPDL1 (7.93 vs. 14.10 months, HR 1.891 (1.35-2.65), p<0.001). In multivariate analysis, high sPDL1 and NLR were independent poor prognostic factors. In conclusion, serum sPDL1 can be measured and has significant role on the prognosis of advanced BTC patients treated with palliative chemotherapy.