Peng Tian-Shu, He Yong-Heng, Nie Tian, Hu Xiang-Dang, Lu Hai-Yan, Yi Jian, Shuai Yun-Fei, Luo Min
Department of Anorectal Disease, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410005, P.R. China.
Department of Blood and Oncology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China.
Exp Ther Med. 2014 Aug;8(2):430-434. doi: 10.3892/etm.2014.1762. Epub 2014 Jun 6.
Protein phosphatase, Mg/Mn dependent, 1D (PPM1D) has been associated with carcinogenesis. The present study investigated PPM1D expression as a potential biomarker in colorectal cancer (CRC). PPM1D expression was assessed using immunohistochemistry in 368 patients with CRC. The correlation between PPM1D expression, clinicopathological features and prognosis was analyzed. PPM1D small interfering (si)RNA-induced PPM1D silencing was performed in CRC cell lines to assess the effect of PPM1D on tumor cell proliferation and invasion . A total of 68.48% (252/368) of the CRC samples displayed high PPM1D expression. By contrast, only 9.24% (34/368) of the matched non-cancerous tissue samples exhibited high PPM1D expression. High PPM1D expression was correlated with node metastasis (P=0.0024), distant metastasis (P<0.001) and TNM stage (P=0.0016). Kaplan-Meier survival analysis revealed that patients with low PPM1D expression had significantly longer survival than those with high PPM1D expression (P=0.012). Moreover, multivariate analyses demonstrated that high PPM1D expression was an independent prognostic factor for overall survival (hazard ratio = 0.24; 95% confidence interval, 0.13-0.86; P=0.004). Furthermore, PPM1D gene silencing was found to significantly reduce the proliferation and invasion of CRC cells . These findings suggest a role for PPM1D as a prognostic marker and potential therapeutic target in CRC.
镁/锰依赖性蛋白磷酸酶1D(PPM1D)与肿瘤发生有关。本研究调查了PPM1D表达作为结直肠癌(CRC)潜在生物标志物的情况。采用免疫组织化学方法评估了368例CRC患者的PPM1D表达。分析了PPM1D表达与临床病理特征及预后之间的相关性。在CRC细胞系中进行PPM1D小干扰(si)RNA诱导的PPM1D沉默,以评估PPM1D对肿瘤细胞增殖和侵袭的影响。共有68.48%(252/368)的CRC样本显示PPM1D高表达。相比之下,仅9.24%(34/368)的配对非癌组织样本表现出PPM1D高表达。PPM1D高表达与淋巴结转移(P = 0.0024)、远处转移(P < 0.001)和TNM分期(P = 0.0016)相关。Kaplan-Meier生存分析显示,PPM1D低表达患者的生存期明显长于PPM1D高表达患者(P = 0.012)。此外,多因素分析表明,PPM1D高表达是总生存期的独立预后因素(风险比 = 0.24;95%置信区间,0.13 - 0.86;P = 0.004)。此外,发现PPM1D基因沉默可显著降低CRC细胞的增殖和侵袭。这些发现表明PPM1D在CRC中作为预后标志物和潜在治疗靶点的作用。