Higher IGFBP-1 to IGF-1 serum ratio predicts unfavourable survival in patients with nasopharyngeal carcinoma.
Higher IGFBP-1 to IGF-1 serum ratio predicts unfavourable survival in patients with nasopharyngeal carcinoma.
复制标题
较高的 IGFBP-1 与 IGF-1 血清比率预示着鼻咽癌患者的不利生存
DOI：
10.1186/s12885-017-3068-0
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发表时间：
2017-01-31
期刊：
影响因子：
3.8
通讯作者：
Zhang G
中科院分区：
文献类型：
--
作者：
Feng X;Lin J;Xing S;Liu W;Zhang G
胰岛素样生长因子（IGF）系统在癌症的发生发展中起着重要作用。然而，对于IGF系统成分在鼻咽癌（NPC）中的表达及其临床病理意义和预后价值知之甚少。方法采用RayBio人细胞因子抗体阵列定量分析鼻咽癌患者和健康人血浆中sigf系统成分（IGF-1、IGF-2、IGF-1SR、IGFBP-1、IGFBP-2、IGFBP-3、IGFBP-4和IGFBP-6）。采用实时荧光定量pcr法测定9株鼻咽癌细胞株和4株永生化鼻咽癌上皮细胞株中IGFBP-1和IGF-1 mRNA水平，并用western blot法检测IGFBP-1蛋白表达。免疫组化法检测石蜡包埋鼻咽癌组织中IGFBP-1和IGF-1的组织特异性表达。采用ELISA法检测142例鼻咽癌患者和128例健康对照者血清IGFBP-1和IGF-1水平，并探讨其与临床病理参数的相关性。结果细胞因子抗体阵列检测鼻咽癌患者外周血IGFBP-1水平明显高于健康对照组，IGF-1和IGF-2水平明显低于健康对照组（P值分别为0.034、0.012和0.046）。在大多数鼻咽癌细胞系中检测到IGFBP-1表达，但在NPE细胞系中未检测到，与正常细胞的细胞质染色相比，IGFBP-1被证明定位于肿瘤细胞核。重要的是，与肿瘤周围组织相比，IGFBP-1在NPC肿瘤组织中的表达更强。相比之下，除了ebv感染的C666细胞系外，IGF-1在NPC和NPE细胞系中的表达较弱或不存在，并且在肿瘤组织中的表达水平低于肿瘤邻近正常组织。NPCs患者血清IGFBP-1水平明显高于健康对照组（55.23±41.25 μg/ lv）。（32.08±29.73 μg/L，P< 0.001），而鼻咽癌患者血清IGF-1水平明显低于健康对照组（98.14±71.48 μg/ lv）。164.01±92.08 μg/L，P= 0.001)。与对照组相比，鼻咽癌患者的IGFBP-1/IGF-1血清比值显著升高（P= 0.002）。血清IGFBP-1水平及IGFBP-1/IGF-1比值与年龄（P= 0.020； P= 0.016）、WHO病理分级（P= 0.044；P= 0.048）、EB病毒衣壳抗原iga滴度、NPC滴度（P= 0.015； P= 0.016）显著相关。相比之下，血清IGFBP-1水平和IGFBP-1/IGF-1比值升高与较差的RFS （P= 0.046； P= 0.037）和OS （P= 0.038； P= 0.009）显著相关。多因素分析显示，IGFBP-1/IGF-1比值，而不是血清IGFBP-1水平，是不良RFS （P= 0.044）和OS （P= 0.035）的独立危险因素。结论IGFBP-1/IGF-1血清比值升高与鼻咽癌患者预后不良有显著相关性。
BackgroundThe insulin-like growth factor (IGF) system plays an important role in the development and progression of cancer. However, little is known about the expression of the IGF system components and their clinicopathological significance and prognostic value in nasopharyngeal carcinoma (NPC).MethodsIGF system components (IGF-1, IGF-2, IGF-1SR, IGFBP-1, IGFBP-2, IGFBP-3, IGFBP-4 and IGFBP-6) were quantified from the plasma of NPC patients and healthy individuals using the RayBio Human Cytokine Antibody Array. IGFBP-1 and IGF-1 mRNA levels were quantified by real-time qPCR, and protein expression was detected by western blot in nine NPC cell lines and four immortalized nasopharyngeal epithelial (NPE) cell lines. Tissue-specific expression of IGFBP-1 and IGF-1 was detected by immunohistochemistry in paraffin-embedded NPC tissues. ELISA analysis was used to measure the serum levels of IGFBP-1 and IGF-1 in 142 NPC patients and 128 healthy controls and determine potential correlation with clinicopathological parameters.ResultsSignificantly higher levels of circulating IGFBP-1 and lower levels of IGF-1 and IGF-2 were detected in NPC patients compared to healthy controls by Cytokine Antibody Array analyses (P =0.034,0.012, 0.046,respectively). IGFBP-1 expression was detected in the majority of NPC cell lines, but not in NPE cell lines, and was shown to localize to the nucleus of tumour cells, in contrast to the cytoplasmic staining observed in normal cells. Importantly, IGFBP-1 expression was stronger in NPC tumour tissues compared to peritumoural tissues. In contrast, IGF-1 expression was weak or absent in NPC and NPE cell lines, with the exception of the EBV-infected C666 cell line, and was found to be expressed at lower levels in tumour tissues compared to tumour-adjacent normal tissue. Levels of serum IGFBP-1 were shown to be significantly higher in patients with NPCs compared to healthy control individuals (55.23 ± 41.25 μg/Lvs. 32.08 ± 29.73 μg/L,P< 0.001), whereas serum levels of IGF-1 were significantly lower in NPC patients compared to healthy controls (98.14 ± 71.48 μg/Lvs. 164.01 ± 92.08 μg/L,P= 0.001). Consistently, the IGFBP-1/IGF-1 serum ratio was shown to be significantly higher in NPC patients compared to healthy control individuals (P= 0.002). Serum levels of IGFBP-1 and the IGFBP-1/IGF-1 ratio significantly correlated with age (P= 0.020; P= 0.016), WHO histological classification (P= 0.044;P= 0.048), titre of EA (EB Virus Capsid Antigen-IgA) and NPC (P= 0.015; P= 0.016). In contrast, higher IGFBP-1 serum levels and IGFBP-1/IGF-1 ratio significantly correlated with poor RFS (P= 0.046; P= 0.037) and OS (P= 0.038; P= 0.009). Multivariate analysis revealed that the IGFBP-1/IGF-1 ratio, but not serum IGFBP-1 level, represents an independent risk factor for poor RFS (P= 0.044) and OS (P= 0.035).ConclusionsA higher IGFBP-1/IGF-1 serum ratio is significantly associated with poor prognosis in NPC patients.