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非小细胞肺癌中14-3-3σ基因的甲基化及14-3-3σ表达的预后意义

Methylation of 14-3-3σ gene and prognostic significance of 14-3-3σ expression in non-small cell lung cancer.

作者信息

Raungrut Pritsana, Petjaroen Pingpond, Geater Sarayut Lucien, Keeratichananont Warangkana, Phukaoloun Monlika, Suwiwat Supaporn, Thongsuksai Paramee

机构信息

Department of Biomedical Sciences and The Excellent Research Laboratory of Cancer Molecular Biology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.

Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand.

出版信息

Oncol Lett. 2017 Nov;14(5):5257-5264. doi: 10.3892/ol.2017.6881. Epub 2017 Sep 4.

Abstract

Loss of 14-3-3σ expression through DNA methylation has been associated with carcinogenesis and the prognosis for various cancer types. Detection of methylation of the gene in serum may be useful for diagnostic utility. The present study aimed to investigate the correlation between 14-3-3σ methylation level in 36 paired tumor tissues of non-small cell lung cancer (NSCLC) and matched serum using methylation-specific polymerase chain reaction. The prognostic significance of 14-3-3σ expression in 167 NSCLC was also evaluated using immunohistochemistry. Methylation of the 14-3-3σ gene was identified in all samples. The methylation level in the serum (mean 87.7%, range 64.6-100%) was higher compared with tumor (mean 46.7%, range 25.3-56.3%). However, no significant correlation between methylation levels in tissues and serums was observed (Spearman's correlation, -0.036; P=0.837). In the 167 tumor tissues, the majority of the cases (83.8%) exhibited negative expression. Adenocarcinoma is more likely to exhibit negative expression (91.4%) compared with squamous cell carcinoma (70.2%). No significant difference was identified in the overall survival according to 14-3-3σ expression status and 14-3-3σ expression did not demonstrated independent prognostic significance. In conclusion, NSCLC harbors certain levels of 14-3-3σ methylation in the tumor and the sera of patients. The clinical value of serum 14-3-3σ methylation should be further elucidated. Immunohistochemical expression 14-3-3σ protein has limited value on prognostic significance.

摘要

通过DNA甲基化导致的14-3-3σ表达缺失与多种癌症类型的致癌作用及预后相关。检测血清中该基因的甲基化情况可能有助于诊断。本研究旨在采用甲基化特异性聚合酶链反应,调查36对非小细胞肺癌(NSCLC)肿瘤组织及其配对血清中14-3-3σ甲基化水平之间的相关性。还采用免疫组织化学方法评估了167例NSCLC中14-3-3σ表达的预后意义。在所有样本中均检测到14-3-3σ基因的甲基化。血清中的甲基化水平(平均87.7%,范围64.6 - 100%)高于肿瘤组织(平均46.7%,范围25.3 - 56.3%)。然而,未观察到组织和血清中甲基化水平之间存在显著相关性(Spearman相关性,-0.036;P = 0.837)。在167例肿瘤组织中,大多数病例(83.8%)表现为阴性表达。与鳞状细胞癌(70.2%)相比,腺癌更易表现为阴性表达(91.4%)。根据14-3-3σ表达状态,总体生存率未发现显著差异,且14-3-σ表达未显示出独立的预后意义。总之,NSCLC患者的肿瘤组织和血清中存在一定水平的14-3-3σ甲基化。血清14-3-3σ甲基化的临床价值有待进一步阐明。免疫组织化学检测14-3-3σ蛋白表达对预后意义的价值有限。

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