P3H4 is correlated with clinicopathological features and prognosis in bladder cancer

Wangjian Li,Lihong Ye,Yongliang Chen,Peng Chen

doi:10.1186/s12957-018-1507-2

Wangjian Li, Lihong Ye + Show 2 more

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https://doi.org/10.1186/s12957-018-1507-2

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Abstract

BackgroundGenetic alterations play a significant role in the progression of bladder cancer. Identifying novel biomarkers to personalize the therapeutic regimen and evaluate the prognosis of patients with bladder cancer is vital. Prolyl 3-hydroxylase family member 4 (P3H4) is significantly involved in several types of human cancer. However, the effect of P3H4 in bladder cancer remains unknown.MethodsThe mRNA expression of P3H4 was measured in 44 paired tumors and adjacent normal tissues by using real-time reverse transcription-polymerase chain reaction. RNA-Seq data of 389 patients with bladder cancer were downloaded to investigate the effect of P3H4 on bladder cancer from The Cancer Genome Atlas (TCGA) project.ResultsP3H4 was overexpressed in bladder cancer compared with the adjacent normal tissue both in our tissue samples and TCGA samples. The mRNA expression of P3H4 was significantly related to several clinicopathological factors of bladder cancer, including age, race category, histologic grade, tumor histologic subtype, and AJCC stage. The high P3H4 expression group had a shorter overall survival (OS) than the low P3H4 expression group. Univariate Cox regression analysis showed that age, angiolymphatic invasion, lymph node metastasis, tumor histologic subtype, metastasis, AJCC stage, and P3H4 were significantly related to OS. Moreover, multivariate Cox analysis revealed that P3H4, as well as age and AJCC stage, was an independent predictor of poor OS.ConclusionGiven its tumorigenic role, P3H4 may serve as a promising tumor-promoting gene in bladder cancer.

Highlights

Genetic alterations play a significant role in the progression of bladder cancer
Prolyl 3-hydroxylase family member 4 (P3H4) was significantly upregulated in bladder cancer To examine the role of P3H4 in bladder cancer, we investigated the P3H4 expression in 44 primary tumors and their paired adjacent normal tissues using Quantitative real-time polymerase chain reaction (qRT-PCR)
Univariate Cox regression analysis showed that age (hazard ratio (HR) = 1.04, 95% CI = 1.023–1.057, p < 0.001), angiolymphatic invasion (HR = 1.619, 95% CI = 1.177–2.226, p = 0.003), lymph node metastasis (HR = 2.071, 95% CI = 1.47–2.918, p < 0.001), tumor histologic subtype (HR = 0.628, 95% CI = 0.433–0.909, p = 0.014), metastasis (HR = 4.507, 95% CI = 2.131–9.532, p < 0.001), AJCC stage (HR = 1.708, 95% CI = 1.402–2.08, p < 0.001), and P3H4 (HR = 1.504, 95% CI = 1.104–2.048, p = 0.01) were associated with overall survival (OS) (Table 2)

Summary

Introduction

Genetic alterations play a significant role in the progression of bladder cancer. The effect of P3H4 in bladder cancer remains unknown. Bladder cancer is the leading malignancy of the genitourinary system [2]. The median survival of patients with advanced bladder cancer is only about 14 months even after aggressive treatment, including surgery, radiation, and chemotherapy [3]. Cancer progression is a complex process that involves changes in various genes, including oncogenes, tumor suppressor genes, and non-coding sequence. Genetic profiling studies have indicated that many genetic alterations, such as those in TP53, RB1, TSC1, FGFR3, and PIK3CA, play critical roles in bladder cancer [4,5,6,7,8,9,10]

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