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富含亮氨酸重复免疫球蛋白样结构域蛋白与癌症预后

LRIG and cancer prognosis.

作者信息

Lindquist David, Kvarnbrink Samuel, Henriksson Roger, Hedman Håkan

机构信息

Oncology Research Laboratory, Department of Radiation Sciences, Umeå University , Umeå , Sweden.

出版信息

Acta Oncol. 2014 Sep;53(9):1135-42. doi: 10.3109/0284186X.2014.953258. Epub 2014 Sep 2.

Abstract

BACKGROUND

Optimal treatment decisions for cancer patients require reliable prognostic and predictive information. However, this information is inadequate in many cases. Several recent studies suggest that the leucine-rich repeats and immunoglobulin-like domains (LRIG) genes, transcripts, and proteins have prognostic implications in various cancer types.

MATERIAL AND METHODS

Relevant literature was identified on PubMed using the key words lrig1, lrig2, and lrig3. LRIG mRNA expression in cancer versus normal tissues was investigated using the Oncomine database.

RESULTS

The three human LRIG genes, LRIG1, LRIG2, and LRIG3, encode single-pass transmembrane proteins. LRIG1 is a negative regulator of growth factor signaling that has been shown to function as a tumor suppressor in vitro and in vivo in mice. The functions of LRIG2 and LRIG3 are less well defined. LRIG gene and protein expression are commonly dysregulated in human cancer. In early stage breast cancer, LRIG1 copy number was recently shown to predict early and late relapse in addition to overall survival; in nasopharyngeal carcinoma, loss of LRIG1 is also associated with poor survival. LRIG gene and protein expression have prognostic value in breast cancer, uterine cervical cancer, head-and-neck cancer, glioma, non-small cell lung cancer, prostate cancer, and cutaneous squamous cell carcinoma. In general, expression of LRIG1 and LRIG3 is associated with good survival, whereas expression of LRIG2 is associated with poor survival. Additionally, LRIG1 regulates cellular sensitivity to anti-cancer drugs, which indicates a possible role as a predictive marker.

CONCLUSIONS

LRIG gene statuses and mRNA and protein expression are clinically relevant prognostic indicators in several types of human cancer. We propose that LRIG analyses could become important when making informed and individualized clinical decisions regarding the management of cancer patients.

摘要

背景

癌症患者的最佳治疗决策需要可靠的预后和预测信息。然而,在许多情况下,此类信息并不充分。最近的几项研究表明,富含亮氨酸重复序列和免疫球蛋白样结构域(LRIG)的基因、转录本和蛋白质在多种癌症类型中具有预后意义。

材料与方法

在PubMed上使用关键词lrig1、lrig2和lrig3检索相关文献。利用Oncomine数据库研究癌症组织与正常组织中LRIG mRNA的表达情况。

结果

人类的三个LRIG基因,即LRIG1、LRIG2和LRIG3,编码单次跨膜蛋白。LRIG1是生长因子信号传导的负调节因子,已证实在小鼠体内外均发挥肿瘤抑制作用。LRIG2和LRIG3的功能尚不清楚。LRIG基因和蛋白表达在人类癌症中通常失调。最近发现,在早期乳腺癌中,LRIG1拷贝数除了可预测总生存期外,还能预测早期和晚期复发;在鼻咽癌中,LRIG1缺失也与生存率低有关。LRIG基因和蛋白表达在乳腺癌、子宫颈癌、头颈癌、神经胶质瘤、非小细胞肺癌、前列腺癌和皮肤鳞状细胞癌中具有预后价值。一般来说,LRIG1和LRIG3的表达与良好的生存率相关,而LRIG2的表达与生存率低相关。此外,LRIG1调节细胞对抗癌药物的敏感性,这表明其可能作为一个预测标志物。

结论

LRIG基因状态以及mRNA和蛋白表达是几种人类癌症中具有临床相关性的预后指标。我们建议,在对癌症患者的管理做出明智且个体化的临床决策时,LRIG分析可能会变得很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4c9/4438349/8ff762d9eefe/sonc53_1135_f1.jpg

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