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CK20、MAP3K8 和 EIF5A 的过表达与早发性结直肠癌患者的不良预后相关。

Overexpression of CK20, MAP3K8 and EIF5A correlates with poor prognosis in early-onset colorectal cancer patients.

机构信息

Department of Medical Biology, Medical Faculty, Uludag University, Bursa, Turkey.

出版信息

J Cancer Res Clin Oncol. 2013 Apr;139(4):691-702. doi: 10.1007/s00432-013-1372-x. Epub 2013 Jan 16.

Abstract

PURPOSE

Due to ethnic, genetic and environmental factors, the clinical and molecular characteristics of Turkish colorectal cancer (CRC) patients are different from those of Western populations. The aim of this study was to clarify the relevant alterations of gene expression associated with colorectal carcinogenesis in early-onset patients and to identify specific biomarkers that could provide novel therapeutic molecular targets in this population.

METHODS

The expression profiles of 114 different genes were evaluated using mRNA PCR arrays in 39 tumors and 20 surgical margin tissue samples from 39 sporadic CRC patients diagnosed at less than 50 years of age.

RESULTS

The expression levels of IMPDH2, CK20, MAP3K8 and EIF5A were strongly up-regulated in CRC tissues compared with normal colorectal tissues (p < 0.05). The highly significant expression ratios of CK20, MAP3K8 and EIF5A observed in the colorectal tumors of patients predicted recurrence (p < 0.05). The expression of IMPDH2, CK20, MAP3K8 and EIF5A was significantly higher in the tumors of patients with short median survival (log-rank p value < 0.05). Progression-free survival was also significantly increased in patients with low expression of the EIF5A gene compared with those who exhibited high expression of this gene (log-rank p value < 0.05).

CONCLUSION

We demonstrated that high CK20, MAP3K8 and EIF5A expression levels were significant prognostic factors for poor overall survival in CRC patients. Further studies and validations are required; these genes may provide novel therapeutic molecular targets for CRC treatment, as well as new directions for the development of anticancer drugs.

摘要

目的

由于种族、遗传和环境因素的影响,土耳其结直肠癌(CRC)患者的临床和分子特征与西方人群不同。本研究旨在阐明与早发性CRC 患者结直肠发生相关的基因表达变化,并鉴定特定的生物标志物,为该人群提供新的治疗分子靶点。

方法

使用 mRNA PCR 阵列评估了 39 例散发性 CRC 患者(年龄小于 50 岁)的 39 例肿瘤和 20 例手术切缘组织样本中 114 个不同基因的表达谱。

结果

与正常结直肠组织相比,CRC 组织中 IMPDH2、CK20、MAP3K8 和 EIF5A 的表达水平明显上调(p < 0.05)。CK20、MAP3K8 和 EIF5A 在患者结直肠肿瘤中的高显著表达比预测复发(p < 0.05)。IMP2H、CK20、MAP3K8 和 EIF5A 的表达在患者中位生存时间较短的肿瘤中明显更高(对数秩检验 p 值<0.05)。与 EIF5A 基因高表达的患者相比,EIF5A 基因低表达的患者无进展生存期明显增加(对数秩检验 p 值<0.05)。

结论

我们表明,CK20、MAP3K8 和 EIF5A 的高表达水平是 CRC 患者总生存不良的显著预后因素。需要进一步的研究和验证;这些基因可能为 CRC 的治疗提供新的治疗分子靶点,并为抗癌药物的开发提供新的方向。

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