title: PPM1D is a prognostic marker and therapeutic target in colorectal cancer.
abstract: Protein phosphatase, Mg2+/Mn2+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 invasionin vitro. 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 cellsin vitro. These findings suggest a role for PPM1D as a prognostic marker and potential therapeutic target in CRC.
authors.affiliation: Department of Anorectal Disease, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410005, P.R. China.
authors.forename: Tian-Shu
authors.initials: TS
authors.lastname: Peng
authors.affiliation: Department of Anorectal Disease, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410005, P.R. China.
authors.forename: Yong-Heng
authors.initials: YH
authors.lastname: He
authors.affiliation: Department of Blood and Oncology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China.
authors.forename: Tian
authors.initials: T
authors.lastname: Nie
authors.affiliation: Department of Anorectal Disease, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410005, P.R. China.
authors.forename: Xiang-Dang
authors.initials: XD
authors.lastname: Hu
authors.affiliation: Department of Anorectal Disease, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410005, P.R. China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Lu
authors.affiliation: Department of Blood and Oncology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yi
authors.affiliation: Department of Blood and Oncology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Shuai
authors.affiliation: Department of Anorectal Disease, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410005, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Luo
keywords: PPM1D; biomarker; colorectal cancer; prognosis