10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）在结直肠癌中缺失情况的综合分析。
A comprehensive analysis of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) loss in colorectal cancer.
作者信息
Lin Pei-Ching, Lin Jen-Kou, Lin Hung-Hsin, Lan Yuan-Tzu, Lin Chun-Chi, Yang Shung-Haur, Chen Wei-Shone, Liang Wen-Yi, Jiang Jeng-Kai, Chang Shih-Ching
机构信息
Department of Clinical Pathology, Yang-Ming Branch, Taipei City Hospital, Taipei, Taiwan.
Division of Colon and Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, No.201, 2nd section, ShiPai Road, Taipei, Taiwan.
出版信息
World J Surg Oncol. 2015 May 20;13:186. doi: 10.1186/s12957-015-0601-y.
BACKGROUND
Alterations of PTEN, regulator of the PTEN/PI3K-AKT pathway, are common in several types of cancer. This study aimed to do comprehensive analysis of PTEN in colorectal cancer patients.
METHODS
Totally, 198 colorectal cancer patients who received surgery at Taipei Veterans General Hospital from 2006 to 2008 were enrolled. Mutations, loss of protein expression, promoter hypermethylation, and DNA copy number of PTEN were analyzed by sequencing, immunohistochemistry, methylation-specific polymerase chain reaction PCR, and quantitative (QPCR), respectively, and correlated with clinicopathological features and patients' outcome.
RESULTS
Genomic mutations, loss of protein expression, promoter hypermethylation, and decreased DNA copy number of PTEN were found in 4 (2.02 %), 68 (34.3 %), 54 (27.3 %), and 36 (18.2 %) tumors, respectively. Of these 68 tumors with loss expression of PTEN, 34 (50 %) tumors had promoter methylation and 18 (26.5 %) had decreased DNA copy number. All four tumors with PTEN mutations demonstrated loss of PTEN expression. In the stage I disease, frequency of loss of PTEN expression was 20 % and significantly increased to 56.9 % in stage IV disease. Either loss expression of PTEN, PTEN hypermethylation or decreased PTEN copy number was not associated with colorectal cancer (CRC) patients' outcome.
CONCLUSIONS
PTEN alterations were found in up to one-third of colorectal cancers but did not impact CRC patients' prognosis.
背景
PTEN/PI3K-AKT信号通路的调节因子PTEN的改变在多种癌症中很常见。本研究旨在对结直肠癌患者的PTEN进行全面分析。
方法
共纳入了198例2006年至2008年在台北荣民总医院接受手术的结直肠癌患者。分别通过测序、免疫组织化学、甲基化特异性聚合酶链反应（PCR）和定量（QPCR）分析PTEN的突变、蛋白表达缺失、启动子高甲基化和DNA拷贝数，并与临床病理特征及患者预后相关联。
结果
分别在4例（2.02%）、68例（34.3%）、54例（27.3%）和36例（18.2%）肿瘤中发现了PTEN的基因组突变、蛋白表达缺失、启动子高甲基化和DNA拷贝数减少。在这68例PTEN表达缺失的肿瘤中，34例（50%）肿瘤存在启动子甲基化，18例（26.5%）存在DNA拷贝数减少。所有4例PTEN突变的肿瘤均表现出PTEN表达缺失。在I期疾病中，PTEN表达缺失的频率为20%，而在IV期疾病中显著增加至56.9%。PTEN表达缺失、PTEN高甲基化或PTEN拷贝数减少均与结直肠癌（CRC）患者的预后无关。
结论
在高达三分之一的结直肠癌中发现了PTEN改变，但并未影响CRC患者的预后。
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