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神经母细胞瘤患儿基因多态性及血清白细胞介素-6和白细胞介素-8水平与预后的关系

Association of Genetic Polymorphisms and Serum Levels of IL-6 and IL-8 with the Prognosis in Children with Neuroblastoma.

作者信息

Moreno-Guerrero Silvia Selene, Ramírez-Pacheco Arturo, Rocha-Ramírez Luz María, Hernández-Pliego Gabriela, Eguía-Aguilar Pilar, Escobar-Sánchez María Argelia, Reyes-López Alfonso, Juárez-Villegas Luis Enrique, Sienra-Monge Juan José Luis

机构信息

Departamento de Hemato-Oncología, Hospital Infantil de México Federico Gómez, Dr. Márquez No. 162, Col Doctores, Delegación Cuauhtémoc, Ciudad de Mexico 06720, Mexico.

Unidad de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Dr. Márquez No. 162, Col Doctores, Delegación, Cuauhtémoc, Ciudad de Mexico 06720, Mexico.

出版信息

Cancers (Basel). 2021 Jan 30;13(3):529. doi: 10.3390/cancers13030529.

Abstract

There is evidence that high circulating levels of IL-6 and IL-8 are markers of a poor prognosis in various types of cancer, including NB. The participation of these cytokines in the tumor microenvironment has been described to promote progression and metastasis. Our objective was to evaluate the prognostic role of genetic polymorphisms and serum levels of IL-6 and IL-8 in a cohort of Mexican pediatric patients with NB. The detection of the SNPs rs1800795 IL-6 and rs4073 and rs2227306 IL-8 was carried out by PCR-RFLP and the levels of cytokines were determined by the ELISA method. We found elevated circulating levels of IL-8 and IL-6 in NB patients compared to the control group. The genotype frequencies of the rs1800795 IL-6 and rs4073 IL-8 variants were different between the patients with NB and the control group. Likewise, the survival analysis showed that the GG genotypes of rs1800795 IL-6 ( = 0.014) and AA genotypes of rs4073 IL-8 ( = 0.002), as well as high levels of IL-6 ( = 0.009) and IL-8 ( = 0.046), were associated with lower overall survival. We confirmed the impact on an adverse prognosis in a multivariate model. This study suggests that the SNPs rs1800795 IL-6 and rs4073 IL-8 and their serum levels could be promising biomarkers of a poor prognosis, associated with overall survival, metastasis, and a high risk in Mexican children with NB.

摘要

有证据表明,IL-6和IL-8的高循环水平是包括神经母细胞瘤(NB)在内的各种癌症预后不良的标志物。这些细胞因子在肿瘤微环境中的参与已被描述为促进肿瘤进展和转移。我们的目的是评估基因多态性以及IL-6和IL-8血清水平在一组墨西哥儿科NB患者中的预后作用。通过聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测IL-6的单核苷酸多态性(SNP)rs1800795以及IL-8的rs4073和rs2227306,并用酶联免疫吸附测定(ELISA)法测定细胞因子水平。我们发现,与对照组相比,NB患者的IL-8和IL-6循环水平升高。NB患者与对照组之间,IL-6的rs1800795和IL-8的rs4073变体的基因型频率不同。同样,生存分析表明,IL-6的rs1800795的GG基因型(P = 0.014)和IL-8的rs4073的AA基因型(P = 0.002),以及高水平的IL-6(P = 0.009)和IL-8(P = 0.046),均与较低的总生存率相关。我们在多变量模型中证实了其对不良预后的影响。本研究表明,SNP rs1800795 IL-6和rs4073 IL-8及其血清水平可能是预后不良的有前景的生物标志物,与墨西哥儿童NB患者的总生存率、转移及高风险相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31be/7866803/3e58a8a9d67b/cancers-13-00529-g001.jpg

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