Downregulation of CRTAC1 in Urothelial Carcinoma Promotes Tumor Aggressiveness and Confers Poor Prognosis

doi:10.31083/j.fbl2809217

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Title:	Downregulation of CRTAC1 in Urothelial Carcinoma Promotes Tumor Aggressiveness and Confers Poor Prognosis
Authors:	Li, Wei-Ming Chan, Ti-Chun Wei, Yu-Ching Li, Chien-Feng Ke, Hung-Lung Wu, Wen-Jeng Hsu, Chin-Chia Wang, Shao-Chuan Yeh, Cheng-Fa
Contributors:	Kaohsiung Med Univ Hosp, Dept Urol Kaohsiung Med Univ, Coll Med, Sch Med, Dept Urol Kaohsiung Med Univ Gang, Shan Hosp, Dept Urol Minist Hlth, Dept Urol Welf Pingtung Hosp Chi Mei Med Ctr, Dept Med Res Natl Inst Canc Res, Natl Hlth Res Inst Kaohsiung Med Univ, Coll Med, Sch Med, Dept Pathol Kaohsiung Municipal Tatung Hosp, Dept Pathol Chi Mei Med Ctr, Dept Clin Med Kaohsiung Municipal Tatung Hosp, Dept Urol Chi Mei Med Ctr, Dept Chinese Med Chung Shan Med Univ Hosp, Dept Urol Chung Shan Med Univ, Sch Med Chi Mei Med Ctr, Div Gen Internal Med Chia Nan Univ Pharm & Sci, Dept Environm Engn & Sci
Keywords:	urothelial carcinoma bladder cancer UTUC CRTAC1 prognosis
Date:	2023
Issue Date:	2024-12-25 11:03:30 (UTC+8)
Publisher:	IMR PRESS
Abstract:	Background: Cartilage acidic protein 1 (CRTAC1) is a glycosylated calcium-binding extracellular matrix protein. The oncological functions of CRTAC1 in urothelial carcinoma (UC) of the urinary bladder (UB) and upper urinary tract (UT) have not yet been elucidated. Based on the published UBUC transcriptome data, we re-evaluated the differential expression profile of calcium ion binding-related genes (GO:0005509), and we found that CRTAC1 was the most significantly downregulated gene in UBUC progression. Therefore, we analyzed the prognostic value and biological significance of CRTAC1 expression in UC. Methods: We used immunohistochemistry to determine the CRTAC1 expression levels in 340 patients with UTUC and 295 patients with UBUC. The CRTAC1 expression was compared with the clinicopathological characteristics, and the prognostic impact of CRTAC1 on metastasis-free survival (MFS) and disease-specific survival (DSS) was evaluated. To study the biological functions of CRTAC1, the proliferation, migration, invasion, and tube formation abilities of UC-derived cells were evaluated. Results: A low CRTAC1 expression significantly correlated with high tumor stage, high histological grade, perineural invasion, vascular invasion, nodal metastasis, and high mitotic rate (all p < 0.01). Moreover, the CRTAC1 immunoexpression status was an independent prognostic factor for MFS and DSS in UBUC and UTUC patients (all p < 0.001) in the multivariate analysis. The exogenous expression of CRTAC1 suppressed the cell proliferation, invasion, and angiogenesis, and downregulated the matrix metallopeptidase 2 (MMP2) level in BFTC909 and T24 cells. Conclusions: CRTAC1 may participate in progression of UC and serve as a prognostic marker for metastasis. Low CRTAC1 expression was significantly associated with aggressive UC characteristics and worse clinical outcomes. The inclusion of CRTAC1 immunoexpression in the standard pathological variables may optimize the risk stratification of patients.
Relation:	Frontiers in Bioscience-Landmark, v.28, n.9, Article 217
Appears in Collections:	[Offices] 456

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