Ti-Chun Chan1, Chien-Feng Li2, Hung-Lung Ke3, Yu-Ching Wei4, Yow-Ling Shiue5, Ching-Chia Li6, Hsin-Chih Yeh7, Hsiang-Ying Lee8, Steven-K Huang9, Wen-Jeng Wu3, Wei-Ming Li10. 1. Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan. 2. Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan; Natioanl Institute of Cancer Research, National Health Research Institute, Tainan, Taiwan; Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan. 3. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 4. Department of Pathology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 5. Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan. 6. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 7. Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan. 8. Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan. 9. Division of Urology, Chi Mei Medical Center, Tainan, Taiwan. 10. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan. Electronic address: u8401067@yahoo.com.tw.
Abstract
PURPOSE: Inflammatory responses affect each stage of carcinogenesis, from initiation, through invasion, to metastasis. Studies have shown that chronic inflammation induced by environmental and occupational exposures increase the risk of developing urothelial carcinoma (UC). Using a published UC transcriptome (GSE32894), we identified that among genes associated with inflammatory response (GO:0006954), TNFAIP6 was significantly upregulated during UC progression. Therefore, we investigated the association of TNFAIP6 with disease features, metastasis and survival in our well-characterized cohort of UC. METHODS: We determined TNFAIP6 expression in 340 upper urinary tract UCs (UTUC) and 295 urinary bladder UCs (UBUC) using immunohistochemistry and evaluated the results using H-score. TNFAIP6 expression correlated with clinicopathological features, disease-specific survival, and metastasis-free survival. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards model. RESULTS: High TNFAIP6 expression was significantly associated with advanced pathological stage, lymph node metastasis, perineural invasion, vascular invasion, and high mitotic activity. Multivariate analysis identified high TNFAIP6 expression as an independent predictor of disease-specific survival (hazard ratio in UTUC: 2.891, P = 0.003; in UBUC: 2.175, P = 0.017) and metastasis-free survival (hazard ratio in UTUC: 3.803, P < 0.001; in UBUC: 3.845, P < 0.001). CONCLUSION: High TNFAIP6 expression is associated with aggressive clinicopathological features and poor prognosis in UCs, suggesting it may serve as a novel prognosticator and treatment target. TNFAIP6 immunostaining may be used with current pathological examinations for better risk stratification for UCs.
PURPOSE: Inflammatory responses affect each stage of carcinogenesis, from initiation, through invasion, to metastasis. Studies have shown that chronic inflammation induced by environmental and occupational exposures increase the risk of developing urothelial carcinoma (UC). Using a published UC transcriptome (GSE32894), we identified that among genes associated with inflammatory response (GO:0006954), TNFAIP6 was significantly upregulated during UC progression. Therefore, we investigated the association of TNFAIP6 with disease features, metastasis and survival in our well-characterized cohort of UC. METHODS: We determined TNFAIP6 expression in 340 upper urinary tract UCs (UTUC) and 295 urinary bladder UCs (UBUC) using immunohistochemistry and evaluated the results using H-score. TNFAIP6 expression correlated with clinicopathological features, disease-specific survival, and metastasis-free survival. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards model. RESULTS: High TNFAIP6 expression was significantly associated with advanced pathological stage, lymph node metastasis, perineural invasion, vascular invasion, and high mitotic activity. Multivariate analysis identified high TNFAIP6 expression as an independent predictor of disease-specific survival (hazard ratio in UTUC: 2.891, P = 0.003; in UBUC: 2.175, P = 0.017) and metastasis-free survival (hazard ratio in UTUC: 3.803, P < 0.001; in UBUC: 3.845, P < 0.001). CONCLUSION: High TNFAIP6 expression is associated with aggressive clinicopathological features and poor prognosis in UCs, suggesting it may serve as a novel prognosticator and treatment target. TNFAIP6 immunostaining may be used with current pathological examinations for better risk stratification for UCs.