Gain of TPPP as a predictor of progression in patients with bladder cancer

Ying-Hsu Chang; Po-Hung Lin; Chin-Chang Chen; Wen-Hui Weng; Kai-Jie Yu; Chung-Yi Liu; Chin-Hsuan Hsieh; Tzu-Hsuan Chang; I-Hung Shao; Hung-Cheng Kan; Cheng-Keng Chuang; See-Tong Pang

doi:10.3892/etm.2021.10638

Gain of TPPP as a predictor of progression in patients with bladder cancer

Exp Ther Med. 2021 Nov;22(5):1204. doi: 10.3892/etm.2021.10638. Epub 2021 Aug 24.

Authors

Ying-Hsu Chang^{1

2

3}, Po-Hung Lin^{2

3

4}, Chin-Chang Chen², Wen-Hui Weng⁵, Kai-Jie Yu^{2

3

5}, Chung-Yi Liu^{1

2

3}, Chin-Hsuan Hsieh², Tzu-Hsuan Chang², I-Hung Shao^{2

3

4}, Hung-Cheng Kan^{2

3}, Cheng-Keng Chuang^{2

3

4}, See-Tong Pang^{2

3}

Affiliations

¹ Department of Urology, New Taipei Municipal Tucheng Hospital, Chang Gung Memorial Hospital, New Taipei City 236017, Taiwan, R.O.C.
² Division of Urology, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Taoyuan 33305, Taiwan, R.O.C.
³ Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan, R.O.C.
⁴ Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan, R.O.C.
⁵ Department of Chemical Engineering and Biotechnology and Graduate Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei 10608, Taiwan, R.O.C.

Abstract

The present study investigated the role of tubulin polymerization promoting protein (TPPP) in the regulation of bladder cancer (BC) cell proliferation and migration, in addition to the association between TPPP gene copy number amplification and clinicopathological characteristics of BC. TPPP gene amplification was measured in human BC epithelial cells and samples obtained from 52 patients with BC via fluorescence in situ hybridization. TPPP gain was defined as mean TPPP copy number >2.2 per nucleus (cutoff). The neutrophil-to-lymphocyte ratio (NLR) was also obtained from the preoperative data of the patients. For in vitro assays, BC cell lines were transfected with either TPPP small interfering RNAs or scrambled control, following which cell proliferation and migration were determined using Cell Counting Kit-8 and Transwell migration assays, respectively. The percentage of cells with TPPP copy number amplification in the four BC epithelial cell lines (MGH-U1, -U1R, -U3, -U4) examined (86.0-100.0%) was found to be higher compared with that in the normal human uroepithelial cell lines (3.0 and 9.0%). Patients were divided into one- (1.9%), two- (55.8%), three- (7.7%), four- (26.9%) and five-copy (7.7%) types. Results calculated using Fisher's exact test indicated that the gain of TPPP in patients with BC associated significantly with age (P<0.05), advanced histological grade (P<0.001), tumor stage (P<0.05), histological type (P<0.001) and NLR (P<0.05). In MGH-U1R and MGH-U4 cells, cell proliferation and migration were revealed to be significantly lower following TPPP knockdown compared with those in cells transfected with the scrambled control. In conclusion, findings from the present study suggest that TPPP is important for cell proliferation, cell migration and BC progression, such that TPPP copy number assessment would be advised for preoperative urine cytology for urothelial neoplasia diagnosis.

Keywords: bladder cancer; cell migration; cell proliferation; gene copy number; tubulin polymerization promoting protein.

Grants and funding

Funding: The present study was supported by grants from The Chang Gung Memorial Hospital Research Foundation (grant nos. CMRPG3D1101-03, CMRPG3H0551 and the Ministry of Science and Technology (MOST 107-2314-B-182A-018-MY3).