TNFAIP6過度表現對於尿路上皮癌病人預後之影響
李威明1,2,3、吳文正1,3,4、李經家1,3、柯宏龍1,3、韋又菁5、葉信志1,3,4、李香瑩3,4
李健逢6、黃俊農3,4、黃俊雄1,3
高雄醫學大學附設中和紀念醫院泌尿部1; 衛生福利部屏東醫院泌尿科2; 高雄醫學大學醫學系泌尿學科3; 高雄市立大同醫院泌尿科4; 高雄市立大同醫院病理科5; 奇美醫學中心病理部6
The prognostic significance of TNFAIP6 overexpression in patients with urothelial carcinoma
Wei-Ming Li 1,2,3, Wen-Jeng Wu 1,3,4, Ching-Chia Li 1,3, Hung-Lung Ke 1,3, Yu-Ching Wei5, Hsin-Chin Yen1,3,4, Hsiang-Ying Lee3,4, Chien-Feng Li6, Chun-Nung Huang 3,4, Chun-Hsiung Huang 1,3
1Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
2 Department of Urology, Pingtung Hospital, Ministry of Health and Welfare, Executive Yuan, Pingtung, Taiwan
3 Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
4 Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
5 Department of Pathology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
6Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan
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.
Materials and 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).
Conclusions: 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.