PPM1H is an independent prognostic biomarker of non-small cell lung cancer

Wen-Qi Zhang, Jian-Nan Gao, Xiang-Lei Chen,  Xi-Feng Yang

Abstract:

Protein phosphatase 1H (PPM1H) is the metal-dependent protein phosphatase, however, its role in tumorigenesis and tumor progression remains controversial. Non-small-cell lung cancer (NSCLC) is the most common histological type of lung cancer but the expression and clinical significance of PPM1H in NSCLC is unknown. In our study, we detected the mRNA of PPM1H in 25 pairs of NSCLC tissues and their corresponding adjacent tissues with qRT-PCR. Moreover, we investigated PPM1H expression in 474 NSCLC tissues and divided them into subgroups with low and high PPM1H. We further evaluated its correlation with the clinicopathological factors. The correlation between PPM1H and other biomarkers involved in tumor progression including chromosome segregation 1-like protein (CSE1L), p53, and Ki67 was also estimated. In addition, the prognostic significance of PPM1H was investigated by univariate and multivariate analyses. The mRNA levels of PPM1H in NSCLCs were significantly higher than those in tumor-adjacent tissues. Patients with low and high PPM1H expression accounted for 54.64% (259/474) and 45.36% (215/474) respectively in all the NSCLCs. PPM1H expression (p=0.012), patients’ sex (p=0.009), tumor size (p<0.001), histological grade (p=0.026), T stage (p=0.002), N stage (p<0.001), M stage (p=0.011), and TNM stage (p<0.001) were all associated with the poor prognosis. With multivariate analysis, PPM1H was determined as an independent prognostic factor of NSCLC (HR=1.42, 95% CI=1.14–1.75, p=0.001). Moreover, high PPM1H was significantly with high Ki67 (p=0.022), indicating the oncogenic role of PPM1H. PPM1H is an independent prognostic factor indicating an unfavorable prognosis of NSCLC. Our results indicated that PPM1H was an important supplement of NSCLC molecular profile and detecting PPM1H may help recognize the high-risk patients for further treatment.