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LAPTM4B 等位基因*2 与乳腺癌易感性和预后相关。

LAPTM4B allele *2 is associated with breast cancer susceptibility and prognosis.

机构信息

Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.

出版信息

PLoS One. 2012;7(9):e44916. doi: 10.1371/journal.pone.0044916. Epub 2012 Sep 12.

Abstract

BACKGROUND

Lysosome-associated protein transmembrane 4 beta (LAPTM4B) has two alleles named LAPTM4B1 and LAPTM4B2. Allele 1 contains only one copy of a 19-bp sequence at the 5'UTR in the first exon, whereas this sequence of allele2 is duplicated and arrayed as a tandem repeat. Previous studies revealed that LAPTM4B polymorphisms contribute to the risk of certain types of cancers. This study aimed to investigate the polymorphism of LAPTM4B in breast cancer by analysis the correlation of LAPTM4B genotype with breast cancer susceptibility, clinicopathologic features and prognosis.

METHODS

Genotyping of the LAPTM4B polymorphism was determined by PCR method. The expression levels of LAPTM4B in breast cancer tissues and breast cancer cell lines were determined by quantitative reverse-transcription PCR (qRT-PCR) analysis. The correlation of LAPTM4B genotype with clinicopathologic parameters and prognosis were assessed statistically.

RESULTS

The results of qRT-PCR analysis indicated that LAPTM4B2 was associated with the higher level of LAPTM4B expression compared with the LAPTM4B1 in both breast cancer cell lines and breast cancer tissues. We found that LAPTM4B2 was associated with an increased risk for breast cancer. LAPTM4B2 was significantly associated with higher histopathologic grade, lymph node metastasis and poor prognosis.

CONCLUSION

LAPTM4B2 is a risk factor associated with breast cancer susceptibility and poor prognosis. LAPTM4B2 may be a potential predicative marker for the susceptibility, progression and metastasis of breast cancer.

摘要

背景

溶酶体相关蛋白跨膜 4β(LAPTM4B)有两个等位基因,分别命名为 LAPTM4B1 和 LAPTM4B2。等位基因1 在第一个外显子的 5'UTR 中只含有一个 19 碱基对序列的拷贝,而等位基因2 的这个序列则重复并串联排列。先前的研究表明,LAPTM4B 多态性与某些类型的癌症风险有关。本研究旨在通过分析 LAPTM4B 基因型与乳腺癌易感性、临床病理特征和预后的相关性,来研究 LAPTM4B 多态性在乳腺癌中的作用。

方法

采用 PCR 方法检测 LAPTM4B 多态性的基因型。采用实时定量逆转录 PCR(qRT-PCR)分析检测乳腺癌组织和乳腺癌细胞系中 LAPTM4B 的表达水平。采用统计学方法评估 LAPTM4B 基因型与临床病理参数和预后的相关性。

结果

qRT-PCR 分析结果表明,与 LAPTM4B1 相比,LAPTM4B2 在乳腺癌细胞系和乳腺癌组织中均与 LAPTM4B 的表达水平升高相关。我们发现 LAPTM4B2 与乳腺癌发病风险增加相关。LAPTM4B2 与较高的组织学分级、淋巴结转移和不良预后显著相关。

结论

LAPTM4B2 是与乳腺癌易感性和不良预后相关的危险因素。LAPTM4B2 可能是预测乳腺癌易感性、进展和转移的潜在标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f242/3440355/7789f06d746f/pone.0044916.g001.jpg

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