EPIC Norfolk 研究中结直肠癌中 PTEN 和 PIK3CA 的改变：与临床病理和饮食因素的关联。
Alterations in PTEN and PIK3CA in colorectal cancers in the EPIC Norfolk study: associations with clinicopathological and dietary factors.
机构信息
Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
出版信息
BMC Cancer. 2011 Apr 7;11:123. doi: 10.1186/1471-2407-11-123.
BACKGROUND
The PTEN tumour suppressor gene and PIK3CA proto-oncogene encode proteins which contribute to regulation and propagation of signal transduction through the PI3K/AKT signalling pathway. This study investigates the prevalence of loss of PTEN expression and mutations in both PTEN and PIK3CA in colorectal cancers (CRC) and their associations with tumour clinicopathological features, lifestyle factors and dietary consumptions.
METHODS
186 adenocarcinomas and 16 adenomas from the EPIC Norfolk study were tested for PTEN and PIK3CA mutations by DNA sequencing and PTEN expression changes by immunohistochemistry. Dietary and lifestyle data were collected prospectively using seven day food diaries and lifestyle questionnaires.
RESULTS
Mutations in exons 7 and 8 of PTEN were observed in 2.2% of CRC and PTEN loss of expression was identified in 34.9% CRC. Negative PTEN expression was associated with lower blood low-density lipoprotein concentrations (p = 0.05). PIK3CA mutations were observed in 7% of cancers and were more frequent in CRCs in females (p = 0.04). Analysis of dietary intakes demonstrated no link between PTEN expression status and any specific dietary factor. PTEN expression negative, proximal CRC were of more advanced Dukes' stage (p = 0.02) and poor differentiation (p < 0.01). Testing of the prevalence of PIK3CA mutations and loss of PTEN expression demonstrated that these two events were independent (p = 0.55).
CONCLUSION
These data demonstrated the frequent occurrence (34.9%) of PTEN loss of expression in colorectal cancers, for which gene mutations do not appear to be the main cause. Furthermore, dietary factors are not associated with loss of PTEN expression. PTEN expression negative CRC were not homogenous, as proximal cancers were associated with a more advanced Dukes' stage and poor differentiation, whereas distal cancers were associated with earlier Dukes' stage.
背景
PTEN 肿瘤抑制基因和 PIK3CA 原癌基因编码的蛋白质有助于调节和传播通过 PI3K/AKT 信号通路的信号转导。本研究调查了在结直肠癌 (CRC) 中 PTEN 表达缺失和 PTEN 和 PIK3CA 突变的发生率及其与肿瘤临床病理特征、生活方式因素和饮食摄入的关系。
方法
通过 DNA 测序检测来自 EPIC Norfolk 研究的 186 例腺癌和 16 例腺瘤中的 PTEN 和 PIK3CA 突变，并用免疫组化检测 PTEN 表达变化。通过 7 天食物日记和生活方式问卷前瞻性收集饮食和生活方式数据。
结果
PTEN 外显子 7 和 8 的突变在 2.2%的 CRC 中观察到，PTEN 表达缺失在 34.9%的 CRC 中被识别。PTEN 表达阴性与较低的血液低密度脂蛋白浓度相关（p=0.05）。PIK3CA 突变在 7%的癌症中观察到，在女性 CRC 中更为常见（p=0.04）。饮食摄入分析表明，PTEN 表达状态与任何特定的饮食因素之间没有联系。PTEN 表达阴性、近端 CRC 的 Dukes 分期更高（p=0.02）和分化较差（p<0.01）。检测 PIK3CA 突变和 PTEN 表达缺失的患病率表明，这两个事件是独立的（p=0.55）。
结论
这些数据表明，PTEN 表达缺失在结直肠癌中频繁发生（34.9%），基因突变似乎不是主要原因。此外，饮食因素与 PTEN 表达缺失无关。PTEN 表达阴性的 CRC 并不均匀，因为近端癌症与更晚期的 Dukes 分期和较差的分化相关，而远端癌症与更早的 Dukes 分期相关。
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