PTP4A3的過度表現與尿路上皮癌的轉移與預後呈顯著相關
葉信志1,2,3、吳文正1,2,3、李經家1,2,3、黃俊農2、柯宏龍2,3、李威明2,3,4、李健逢5、李香瑩1,2,3
1高雄市立大同醫院 泌尿科；2高雄醫學大學附設中和紀念醫院 泌尿科；3高雄醫學大學 醫學研究所；4衛生福利部屏東醫院 泌尿科；5奇美醫學中心 病理科
Overexpression of PTP4A3 is associated with metastasis and unfavorable prognosis in urothelial carcinoma
Hsin-Chih Yeh1,2,3, Wen-Jeng Wu1,2,3, Ching-Chia Li1,2,3, Chun-Nung Huang2, Hung-Lung Ke2,3, Wei-Ming Li2,3,4, Chien-Feng Li5, Hsiang-Ying Lee1,2,3
1Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; 2Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 3Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Department of Urology, Ministry of Health and Welfare Pingtung Hospital, Pingtung, Taiwan; 5Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan
Purpose: Urothelial carcinoma (UC) is the most common malignancy involving urinary bladder (UB) and upper urinary tract (UT) for which the theranostic markers remain under-investigated. Increasing evidence has shown that protein tyrosine phosphatases (PTPs) play dominant roles in setting the levels of tyrosine phosphorylation and promote oncogenic processes. However, their expression has not been systemically investigated in UC, and our aim is to examine their potential impact on UC.
Materials and Methods: We performed data mining from a published transcriptome of UBUCs (GSE32894), and PTP type IVA member 3 (PTP4A3) was identified as the most significantly upregulated gene among those related to prenylated PTP activity (GO: 0004727). The importance of PTP4A3 was initially analyzed in paired normal urothelium, non-invasive UC, invasive UC, and nodal metastatic tissue. PTP4A3 transcript level was assessed in snap-frozen UC samples by laser capture microdissection and real-time RT-PCR. PTP4A3 protein expression was determined by immunohistochemistry in 295 UBUCs and 340 UTUCs, respectively. The association of PTP4A3 expression with clinicopathological features, disease-specific survival (DSS), and metastasis-free survival (MeFS) was further evaluated.
Results: For both UBUC and UTUC, the level of PTP4A3 significantly increased from normal urothelium, non-invasive UC, invasive UC, to nodal metastatic tissue (both p <0.001). The PTP4A3 transcript level was also markedly upregulated in high stage UC (UBUC, p <0.001; UTUC, p = 0.002). Overexpression of PTP4A3 protein was significantly associated with advanced pT status, nodal metastasis, and lymphovascular invasion (all p <0.001). PTP4A3 overexpression not only predicted worse DSS and MeFS on univariate analysis (all p <0.001), but also implicated in inferior DSS (UBUC, p <0.001; UTUC, p = 0.001) and MeFS (UBUC, p = 0.003; UTUC, p = 0.001) on multivariate analysis.
Conclusions: PTP4A3 overexpression independently predicted metastasis and outcome of both UBUC and UTUC, suggesting its potential theranostic value in UC.