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中性粒细胞与淋巴细胞比值、血清细胞因子及血管生成因子检测的抗肿瘤免疫在胃癌中的预后意义

Prognostic implication of antitumor immunity measured by the neutrophil-lymphocyte ratio and serum cytokines and angiogenic factors in gastric cancer.

作者信息

Ock Chan-Young, Nam Ah-Rong, Lee Joongyub, Bang Ju-Hee, Lee Kyung-Hun, Han Sae-Won, Kim Tae-Yong, Im Seock-Ah, Kim Tae-You, Bang Yung-Jue, Oh Do-Youn

机构信息

Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.

Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

出版信息

Gastric Cancer. 2017 Mar;20(2):254-262. doi: 10.1007/s10120-016-0613-5. Epub 2016 May 5.

DOI:10.1007/s10120-016-0613-5
PMID:27147244
Abstract

BACKGROUND

The neutrophil-lymphocyte ratio (NLR) is associated with a poor prognosis in many cancers but the biological mechanisms involved are unknown. Since cytokines and angiogenic factors (CAFs) are reflected by various immune responses, we analyzed the association between the NLR and CAFs and their prognostic implications in gastric cancer (GC).

METHODS

Of 745 GC patients who were enrolled in NLR analysis, 70 underwent NLR and CAF association analyses. Pretreatment serum levels of 52 CAFs were measured by means of multiplex bead immunoassays and enzyme-linked immunosorbent assays. Linear regression analysis and survival analysis of the NLR with each CAF were performed.

RESULTS

Metastatic organ numbers and carbohydrate antigen 19-9 levels were significantly higher in patients with a high NLR [greater than 2.42 (median): P = 0.047 and P < 0.001 respectively]. The overall survival was significantly worse in the high NLR group (17.8 months vs 11.2 months, P < 0.001). In CAF analysis, osteopontin (R  = 0.337, P < 0.001) and interleukin-6 (R  = 0.141, P = 0.001) were significantly associated with the NLR. Stromal-cell-derived factor 1 (SDF-1) was a significant poor prognostic factor independently of the NLR. Consideration of both the NLR and SDF-1 divided patient groups with different overall survival (both low, 21.0 months; either high, 15.8 months; both high, 8.2 months).

CONCLUSION

The NLR is a significant poor prognostic factor in advanced GC. The NLR is mainly associated with osteopontin and interleukin-6. Besides the NLR, SDF-1 is an independent poor prognostic factor in GC. Consideration of both the NLR and SDF-1 might give insights into antitumor immunity in GC.

摘要

背景

中性粒细胞与淋巴细胞比值(NLR)在许多癌症中与预后不良相关,但其中涉及的生物学机制尚不清楚。由于细胞因子和血管生成因子(CAFs)可通过各种免疫反应反映出来,我们分析了NLR与CAFs之间的关联及其在胃癌(GC)中的预后意义。

方法

在纳入NLR分析的745例GC患者中,70例进行了NLR与CAF关联分析。通过多重微珠免疫测定和酶联免疫吸附测定法检测52种CAFs的预处理血清水平。对NLR与每种CAF进行线性回归分析和生存分析。

结果

NLR高的患者(大于2.42(中位数))转移器官数量和糖类抗原19-9水平显著更高(分别为P = 0.047和P < 0.001)。高NLR组的总生存期显著更差(17.8个月对11.2个月,P < 0.001)。在CAF分析中,骨桥蛋白(R = 0.337,P < 0.001)和白细胞介素-6(R = 0.141,P = 0.001)与NLR显著相关。基质细胞衍生因子1(SDF-1)是独立于NLR的显著不良预后因素。同时考虑NLR和SDF-1可将患者分为总生存期不同的组(两者均低,21.0个月;任一高,15.8个月;两者均高,8.2个月)。

结论

NLR是晚期GC的显著不良预后因素。NLR主要与骨桥蛋白和白细胞介素-6相关。除NLR外,SDF-1是GC的独立不良预后因素。同时考虑NLR和SDF-1可能有助于深入了解GC中的抗肿瘤免疫。

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