WISP1 genetic variants as predictors of tumor development with urothelial cell carcinoma

Urothelial cell carcinoma (UCC) of the urinary bladder is a major malignancy of the genitourinary tract. Etiological factors, such as the environment, ethnicity, genetics, and diet, contribute to UCC carcinogenesis. WNT1-inducible signaling pathway protein 1 (WISP1), also known as CCN4, a cysteine-rich protein belonging to the Cyr61, CTGF, Nov (CCN) family of matricellular proteins, has many developmental functions and might be involved in carcinogenesis. This study investigated WISP1 single-nucleotide polymorphisms to evaluate UCC susceptibility and clinicopathological characteristics.

Real-time polymerase chain reaction was used to analyze 4 single-nucleotide polymorphisms of WISP1 in 369 patients with UCC and 738 controls without cancer.

The results showed that in 128 women with UCC who carried WISP1 rs2929973 (AG + GG) variants had a higher risk of developing an advanced muscle-invasive tumor stage (pT2-pT4, P = 0.007) and a large tumor (T1-T4, P = 0.030). Further analyses revealed that a correlation between the expressions of WISP1 and invasive tumor and large tumor size in urothelial carcinoma was observed in the TCGA (The Cancer Genome Atlas) dataset.

Our results indicated that patients with UCC carrying rs2977530 genetic variants (AG + GG) have a higher risk of developing a more invasive tumor stage and a large tumor. WISP1 polymorphisms may serve as a marker or a therapeutic target in UCC.

Urologic oncology. 2017 Dec 22 [Epub ahead of print]

Hsiang-Lin Lee, Hui-Ling Chiou, Shian-Shiang Wang, Sheng-Chun Hung, Ming-Chih Chou, Shun-Fa Yang, Ming-Ju Hsieh, Ying-Erh Chou

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan., School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan; Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan., Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan., Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan., Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan., Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan. Electronic address: ., School of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan. Electronic address: .