HAS3 underexpression as an indicator of poor prognosis in patients with urothelial carcinoma of the upper urinary tract and urinary bladder.
Via data mining a published transcriptomic database of UBUC (GSE31684), we discovered hyaluronan synthase-3 (HAS3) as the most significant gene stepwise downregulated from early tumorigenesis to progression among those associated with hyaluronan synthase activity (GO:0050501). We consequently analyzed HAS3 protein expression and their association with clinicopathological factors and survival in our well-characterized cohort of urothelial carcinoma of upper urinary tract (UTUC) and urinary bladder (UBUC). HAS3 expression was assessed by immunohistochemistry and evaluated by using H score method in 295 UBUCs and 340 UTUCs, respectively. HAS3 protein expression statuses were further correlated with clinicopathological parameters and evaluated the prognostic significance for disease-specific survival (DSS) and metastasis-free survival (MeFS). HAS3 protein underexpression was significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular invasion, and frequent mitoses in both groups of UCs. HAS3 underexpression not only predicted poorer DSS and MeFS with univariate analysis, but also indicated dismal DSS and MeFS in multivariate analysis. HAS3 underexpression is associated with advanced tumor stage and adverse pathological features, as well as implies inferior clinical outcomes for both groups of patients with UTUCs and UBUCs, suggesting its critical role in tumor progression in UCs and may serve as a prospective prognostic biomarker and a novel therapeutic target in UCs.
Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan.
I-Wei
IW
Chang
Peir-In
PI
Liang
Ching-Chia
CC
Li
Wen-Jeng
WJ
Wu
Chun-Nung
CN
Huang
Victor Chia-Hsiang
VC
Lin
Chao-Tien
CT
Hsu
Hong-Lin
HL
He
Ting-Feng
TF
Wu
Chih-Hsin
CH
Hung
Chien-Feng
CF
Li
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D014453:Glucuronosyltransferase / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D000076002:Hyaluronan Synthases; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D014551:Urinary Tract / Q000473:pathology*; D019459:Urothelium / Q000473:pathology
D014408:Biomarkers, Tumor; D014453:Glucuronosyltransferase; C105458:HAS3 protein, human; D000076002:Hyaluronan Synthases