J Cancer 2019; 10(25):6207-6216. doi:10.7150/jca.37335

Research Paper

p53/PCDH17/Beclin-1 Proteins as Prognostic Predictors for Urinary Bladder Cancer

Liuxi Chen1,2*, Ying Liu1*, Qi Zhang4*, Mingming Zhang2, Xuemeng Han2, Qiujie Li2, Tian Xie2,3✉, Qibiao Wu5✉, Xinbing Sui1,2,3✉

1. Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
2. Holistic Integrative Pharmacy Institutes and Comprehensive Cancer Diagnosis and Treatment Center, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China
3. Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, China
4. Department of Urology and Institute of Department of Urology, Zhejiang Provincial People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
5. State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, P.R. China
*These authors contributed equally to this work

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Citation:
Chen L, Liu Y, Zhang Q, Zhang M, Han X, Li Q, Xie T, Wu Q, Sui X. p53/PCDH17/Beclin-1 Proteins as Prognostic Predictors for Urinary Bladder Cancer. J Cancer 2019; 10(25):6207-6216. doi:10.7150/jca.37335. Available from http://www.jcancer.org/v10p6207.htm

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Abstract

Purpose: To determine whether p53, PCDH17, Beclin-1 expression is associated with clinicopathological characteristics of bladder cancer.

Materials and Methods: 75 patients with non-muscle-invasive and muscle-invasive bladder cancer were included. Immunohistochemical staining for p53, PCDH17 and Beclin-1 were carried out on the same paraffin-embedded blocks serial sections of these patients who underwent surgery between 2010 and 2015. In addition, p53 gene mutations in these tumors were screened by DNA sequencing.

Results: Forty-nine (66.7%) of 75 tumors had p53 gene mutations detected by DNA sequencing method. Of these tumors, 43 (86.0%) exhibited p53 high expression. Furthermore, p53 mutation and low expression of PCDH17 were significantly associated with muscle-invasive bladder cancer. Beclin-1 was also strongly associated with T stage. The p53 mutation, the expression of p53 and PCDH17 were significantly associated with survival from bladder cancer. In addition, patients with p53 high-expression or p53 mutation, PCDH17 low-expression and Beclin-1 low-expression significantly had a poor prognosis.

Conclusions: Use of a DNA sequencing method to detect p53 gene mutations was consistent with an immunohistochemical method to detect p53 alterations. In conjunction with levels of p53/PCDH17/Beclin-1, p53 and PCDH17 were independently associated with prognosis; Beclin-1 only had a tendency towards overall survival. p53/PCDH17/Beclin-1 phenotype seems to play a more important role than p53 expression in bladder cancer outcome. It is also identified that p53/PCDH17, p53/Beclin-1 or PCDH17/Beclin-1 all have a cooperative and synergistic effect, which may provide us the potential biomarker for bladder cancer patients.

Keywords: p53, protocadherin 17, Beclin-1, Urinary bladder neoplasms