Prospective validation of DACH2 as a novel biomarker for prediction of metastasis and prognosis in muscle-invasive urothelial carcinoma of the bladder.
Metastasis is the main cause of death from muscle-invasive urothelial carcinoma of the bladder (UCB), and the metastatic potential of tumors is often unpredictable. The role of Dachshund homolog 2 gene (DACH2) in tumorigenesis remains unexplored. We aimed to investigate whether DACH2 can be used as a biomarker to predict metastasis and prognosis of muscle-invasive UCB in a sequential training and validation fashion. For the training set (n = 40), compared with UCB patients without lymph node (LN) metastasis, both DACH2 protein and mRNA expression were greatly increased in case-matched patients with LN metastasis. For the independent validation set (n = 243), patients with primary UCB that did not express DACH2 had a longer metastasis-free survival (MFS) and overall survival (OS) than did those with tumors expressing DACH2 (5-year MFS: 88% [95% CI 80-96] versus 19% [95% CI 7-31], p < 0.001; 5-year OS: 93% [95% CI 87-99] versus 37% [95% CI 23-51], p < 0.001). Multivariable analysis of DACH2 status showed hazard ratios of 7.34 (95% CI 3.15-11.87, p < 0.001) for MFS and 3.96 (95% CI 2.04-7.16, p < 0.001) for OS which were much higher than hazard ratios associated with other independent risk factors. Collectively, DACH2 is an independent prognostic marker that can be used at initial diagnosis of UCB to identify patients who have a high potential to develop metastasis.
Center of Health Care, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Ya-Di
YD
He
Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Zi-Huan
ZH
Luo
Department of Urology, Foshan Hospital of Traditional Medicine, Foshan, 528000, China.
Ming
M
Yang
Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Xing-Xing
XX
Ruan
Department of Urology, Foshan First Municipal People's Hospital, Sun Yat-sen University, Foshan, 528000, China.
Shao-Yuan
SY
Liu
Department of Urology, Foshan First Municipal People's Hospital, Sun Yat-sen University, Foshan, 528000, China.
Zhen-Quan
ZQ
Wu
Department of Urology, The First Affiliated Hospital, University of South China, Hengyang, 421000, China.
Wei-Ming
WM
Deng
Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Chun-Kui
CK
Shao
Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Zu-Lan
ZL
Su
Department of Pathology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Dan
D
He
Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
Xin
X
Gao
Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China. Electronic address: liliao10318023@126.com.
Liao-Yuan
LY
Li
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary*
D014408:Biomarkers, Tumor; C403064:DACH2 protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors
Bladder cancer; Dachshund homolog 2 gene; Immunohistochemistry; Prognosis; Radical cystectomy