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人类结肠癌中IFRD1表达增加预示患者生存率降低。

Increased IFRD1 Expression in Human Colon Cancers Predicts Reduced Patient Survival.

作者信息

Lewis Mark A, Sharabash Noura, Miao Zhi-Feng, Lyons Lydia N, Piccirillo Jay, Kallogjeri Donna, Schootman Mario, Mutch Matthew, Yan Yan, Levin Marc S, Castells Antoni, Cuatrecasas Miriam, Mills Jason C, Wang Zhen-Ning, Rubin Deborah C

机构信息

Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, Box 8124, St. Louis, MO, 63110, USA.

University of Illinois, Carle Clinics, 611 W. Park Street, Urbana, IL, 61801, USA.

出版信息

Dig Dis Sci. 2017 Dec;62(12):3460-3467. doi: 10.1007/s10620-017-4819-0. Epub 2017 Nov 1.

Abstract

BACKGROUND

Colon cancer (CRC) is the third most common cancer worldwide. CRC develops through combinations of genetic and epigenetic changes. However, there is marked heterogeneity in the "driver gene" mutational profiles within and among colon cancers from individual patients, and these are not sufficient to explain differences in colon cancer behavior and treatment response. Global modulation of the tumor landscape may play a role in cancer behavior. Interferon-related developmental regulator 1 (IFRD1) is a transcriptional co-regulator that modulates expression of large gene cassettes and plays a role in gut epithelial proliferation following massive intestinal resection.

AIMS

We address the hypothesis that increased IFRD1 expression in colon cancers is associated with poorer patient survival.

METHODS

Tumor and normal tissue from colon cancer patient cohorts from the USA, Spain, and China were used for this study. Cancers were scored for the intensity of IFRD1 immunostaining. The primary clinical outcome was overall survival defined as time from diagnosis to death due to cancer. Kaplan-Meier method and log-rank analysis were used to assess the association between IFRD1 expression and survival.

RESULTS

Almost all (98.7%) colon cancers showed readily detectable IFRD1 expression, with immunoreactivity primarily in the tumor cytoplasm. High IFRD1 colon cancer expression was significantly associated with decreased 5-year patient survival. Patients in the American cohort with high IFRD1 expression had a poorer prognosis.

CONCLUSIONS

We have demonstrated that high IFRD1 protein expression in colon cancer is associated with poorer patient prognosis, suggesting a potential role for IFRD1 in modulating tumor behavior.

摘要

背景

结肠癌(CRC)是全球第三大常见癌症。CRC通过基因和表观遗传变化的组合发展而来。然而,个体患者结肠癌内部和之间的“驱动基因”突变谱存在显著异质性,这些不足以解释结肠癌行为和治疗反应的差异。肿瘤格局的全局调节可能在癌症行为中起作用。干扰素相关发育调节因子1(IFRD1)是一种转录共调节因子,可调节大基因盒的表达,并在大规模肠切除术后的肠道上皮增殖中起作用。

目的

我们探讨结肠癌中IFRD1表达增加与患者较差生存率相关的假设。

方法

本研究使用了来自美国、西班牙和中国的结肠癌患者队列的肿瘤和正常组织。对癌症进行IFRD1免疫染色强度评分。主要临床结局是总生存期,定义为从诊断到因癌症死亡的时间。采用Kaplan-Meier法和对数秩分析来评估IFRD1表达与生存率之间的关联。

结果

几乎所有(98.7%)结肠癌都显示出易于检测到的IFRD1表达,免疫反应主要在肿瘤细胞质中。高IFRD1结肠癌表达与患者5年生存率降低显著相关。美国队列中IFRD1表达高的患者预后较差。

结论

我们已经证明结肠癌中高IFRD1蛋白表达与患者较差的预后相关,提示IFRD1在调节肿瘤行为中可能发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2873/6167971/391b09482405/nihms-950033-f0001.jpg

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