瑞典患者中[具体内容未给出]的蛋白质表达、基因变异及其与结直肠癌的关联

Protein Expression and Genetic Variation of and Association with Colorectal Cancer in Swedish Patients.

作者信息

Shamoun Levar, Kolodziej Blanka, Andersson Roland E, Dimberg Jan

机构信息

Division of Medical Diagnostics, Department of Laboratory Medicine, Jönköping County, Jönköping, Sweden.

Department of Pathology, Jönköping County, Jönköping, Sweden.

出版信息

Anticancer Res. 2018 Jan;38(1):321-328. doi: 10.21873/anticanres.12225.

DOI:10.21873/anticanres.12225

PMID:29277790

Abstract

BACKGROUND

Interleukin 32 (IL32) is an intracellular pluripotent cytokine produced by epithelial cells, monocytes, T-lymphocytes and natural killer cells and seems to be involved in the pathogenesis of cancer and inflammatory diseases. Our purpose was to assess the role of protein expression and genetic polymorphisms of IL32 in colorectal cancer (CRC) susceptibility.

MATERIALS AND METHODS

To gain insight into clinical significance of IL32 in Swedish patients with CRC, using enzyme-linked immunosorbent assay, we determined whether IL32 protein level is altered in CRC tissue (n=75) compared with paired normal tissue and in plasma from patients with CRC (n=94) compared with controls (n=81). The expression of IL32 protein was confirmed by immunohistochemistry (n=73). We used Luminex technology to investigate protein levels of the cytokines IL6, tumor necrosis factor-α (TNFα) and vascular endothelial growth factor (VEGF) to relate these to IL32 levels in CRC tissue. Three single nucleotide polymorphisms (SNPs) (rs28372698, rs12934561, rs4786370) of the IL32 gene have been proposed as modifiers for different diseases. The present study evaluated the susceptibility of patients possessing these SNPs to CRC. Using TaqMan SNP genotyping assays, these SNPs were screened in Swedish patients with CRC (n=465) and healthy controls (n=331).

RESULTS

We found no significant differences in the genotypic frequencies between the patients and healthy controls and no relation to survival for any of the SNPs. However, the SNP rs12934561 was statisticalLY significant associated with older patients. IL32 protein was up-regulated in CRC tissue and related to IL6, TNFα, and VEGF, and seems to be modulated by SNP rs28372698. The IL32 protein level in CRC tissue also reflects both disseminated disease and location.

CONCLUSION

Our results suggest that altered IL32 protein concentrations in CRC tissue and genotypic variants of IL32 are related to disseminated CRC.

摘要

背景

白细胞介素32（IL32）是一种由上皮细胞、单核细胞、T淋巴细胞和自然杀伤细胞产生的细胞内多能细胞因子，似乎参与癌症和炎症性疾病的发病机制。我们的目的是评估IL32蛋白表达和基因多态性在结直肠癌（CRC）易感性中的作用。

材料与方法

为深入了解IL32在瑞典CRC患者中的临床意义，我们采用酶联免疫吸附测定法，确定CRC组织（n = 75）与配对正常组织相比以及CRC患者血浆（n = 94）与对照组（n = 81）相比，IL32蛋白水平是否发生改变。通过免疫组织化学（n = 73）证实了IL32蛋白的表达。我们使用Luminex技术研究细胞因子IL6、肿瘤坏死因子-α（TNFα）和血管内皮生长因子（VEGF）的蛋白水平，以将这些与CRC组织中的IL32水平相关联。IL32基因的三个单核苷酸多态性（SNP）（rs28372698、rs12934561、rs4786370）已被认为是不同疾病的修饰因子。本研究评估了携带这些SNP的患者对CRC的易感性。使用TaqMan SNP基因分型测定法，在瑞典CRC患者（n = 465）和健康对照（n = 331）中筛选这些SNP。

结果

我们发现患者与健康对照之间的基因型频率没有显著差异，且任何SNP与生存率均无关联。然而，SNP rs12934561与老年患者在统计学上显著相关。IL32蛋白在CRC组织中上调，与IL6、TNFα和VEGF相关，并且似乎受SNP rs28372698调节。CRC组织中的IL32蛋白水平也反映了播散性疾病和肿瘤位置。