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 invasion in 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 cells in vitro. These findings suggest a role for PPM1D as a prognostic marker and potential therapeutic target in CRC.
Highlights
IntroductionColorectal cancer (CRC) mortality accounts for ~9% of all cancer mortalities [2]
Colorectal cancer (CRC) is the third most common cancer in humans worldwide [1]
The present study investigated the correlation between PPM1D expression, survival and clinical and pathological features in patients with CRC
Summary
CRC mortality accounts for ~9% of all cancer mortalities [2]. Available cancer markers are not suitable for current clinical practice and require further investigation. There is an urgent requirement for the discovery of novel targets and useful biomarkers for CRC prognosis. Mg2+/Mn2+ dependent, 1D (PPM1D) is a member of the protein phosphatase 2C family and is involved in a wide range of physiological functions, including cell signaling, apoptosis and the cell cycle [4]. PPM1D has been reported to be upregulated in human primary breast, ovarian and neuroblastoma tumors [5,6,7]. The present study investigated the expression pattern and clinical significance of PPM1D in CRC, including the correlation of PPM1D with clinical outcome
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