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CD93基因多态性与播散性结直肠癌相关。

CD93 gene polymorphism is associated with disseminated colorectal cancer.

作者信息

Olsen Renate S, Lindh Mikael, Vorkapic Emina, Andersson Roland E, Zar Niklas, Löfgren Sture, Dimberg Jan, Matussek Andreas, Wågsäter Dick

机构信息

Division of Drug Research, Department of Medical and Health Sciences, Faculty of Health Sciences, University of Linköping, 58185, Linköping, Sweden,

出版信息

Int J Colorectal Dis. 2015 Jul;30(7):883-90. doi: 10.1007/s00384-015-2247-1. Epub 2015 May 26.

Abstract

PURPOSE

Cluster of differentiation 93 (CD93) is involved in apoptosis and inflammation and has a suggested role in angiogenesis, and all of which are involved in the development and dissemination of cancer. We evaluated the expression of CD93 and the association with two single nucleotide polymorphisms (SNPs), rs2749812 and rs2749817, as possible biomarkers in colorectal cancer (CRC).

METHODS

Tissue levels and plasma levels of CD93 were measured using an enzyme-linked immunosorbent assay (ELISA). Expression of CD93 was determined by immunohistochemistry, western blot and gene expression analysis. Genotype frequencies were established for the SNPs by real-time polymerase chain reaction (PCR), and the association with tumour stage and survival was analysed.

RESULTS

Total CD93 levels were 82% higher (P < 0.001) in tumours compared to matched normal tissues. Mean levels of soluble CD93 in plasma were 30% lower (P < 0.001) in the patients compared to the controls. The T/T genotype of SNP rs2749817 was more common in stage IV patients, with consequently higher risk of CRC death (T/T vs. C/C and C/T; hazard ratio (HR) = 1.73, 95% confidence interval (CI) = 1.11-2.67, P = 0.014), and was associated with a higher risk of CRC recurrence after radical operation (T/T vs. C/C and C/T; HR = 2.07, CI = 1.22-3.51, P = 0.007).

CONCLUSIONS

We showed that the T/T genotype of SNP rs2749817 is associated with disseminated cancer at diagnosis and an increased recurrence rate after radical operation. Patients with this genotype may benefit from early identification.

摘要

目的

分化簇93(CD93)参与细胞凋亡和炎症反应,且在血管生成中具有一定作用,而这些都与癌症的发生和扩散有关。我们评估了CD93的表达及其与两个单核苷酸多态性(SNP),即rs2749812和rs2749817的关联,将其作为结直肠癌(CRC)可能的生物标志物。

方法

采用酶联免疫吸附测定(ELISA)法检测CD93的组织水平和血浆水平。通过免疫组织化学、蛋白质印迹法和基因表达分析确定CD93的表达。采用实时聚合酶链反应(PCR)确定SNP的基因型频率,并分析其与肿瘤分期和生存率的关联。

结果

与配对的正常组织相比,肿瘤中的总CD93水平高82%(P < 0.001)。与对照组相比,患者血浆中可溶性CD93的平均水平低30%(P < 0.001)。SNP rs2749817的T/T基因型在IV期患者中更为常见,因此CRC死亡风险更高(T/T与C/C和C/T相比;风险比(HR)= 1.73,95%置信区间(CI)= 1.11 - 2.67,P = 0.014),并且与根治性手术后CRC复发风险较高相关(T/T与C/C和C/T相比;HR = 2.07,CI = 1.22 - 3.51,P = 0.007)。

结论

我们发现SNP rs2749817的T/T基因型与诊断时的播散性癌症以及根治性手术后复发率增加有关。具有这种基因型的患者可能受益于早期识别。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7658/4471320/cf378f0e58f9/384_2015_2247_Fig1_HTML.jpg

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