HuR cytoplasmic expression is associated with increased cyclin A expression and poor outcome with upper urinary tract urothelial carcinoma

Peir In Liang, Wei Ming Li, Yu Hui Wang, Ting Feng Wu, Wen Ren Wu, Alex C. Liao, Kun Hung Shen, Yu Ching Wei, Chung-Hsi Hsing, Yow Ling Shiue, Hsuan Ying Huang, Han Ping Hsu, Li Tzong Chen, Ching Yih Lin, Chein Tai, Chun-Mao Lin, Chien Feng Li

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Abstract

Background: HuR is an RNA-binding protein that post-transcriptionally modulates the expressions of various target genes implicated in carcinogenesis, such as CCNA2 encoding cyclin A. No prior study attempted to evaluate the significance of HuR expression in a large cohort with upper urinary tract urothelial carcinomas (UTUCs).Methods: In total, 340 cases of primary localized UTUC without previous or concordant bladder carcinoma were selected. All of these patients received ureterectomy or radical nephroureterectomy with curative intents. Pathological slides were reviewed, and clinical findings were collected. Immunostaining for HuR and cyclin A was performed and evaluated by using H-score. The results of cytoplasmic HuR and nuclear cyclin A expressions were correlated with disease-specific survival (DSS), metastasis-free survival (MeFS), urinary bladder recurrence-free survival (UBRFS), and various clinicopathological factors.Results: HuR cytoplasmic expression was significantly related to the pT status, lymph node metastasis, a higher histological grade, the pattern of invasion, vascular and perineurial invasion, and cyclin A expression (p = 0.005). Importantly, HuR cytoplasmic expression was strongly associated with a worse DSS (p <0.0001), MeFS (p <0.0001), and UBRFS (p = 0.0370) in the univariate analysis, and the first two results remained independently predictive of adverse outcomes (p = 0.038, relative risk [RR] = 1.996 for DSS; p = 0.027, RR = 1.880 for MeFS). Cyclin A nuclear expression was associated with a poor DSS (p = 0.0035) and MeFS (p = 0.0015) in the univariate analysis but was not prognosticatory in the multivariate analyses. High-risk patients (pT3 or pT4 with/without nodal metastasis) with high HuR cytoplasmic expression had better DSS if adjuvant chemotherapy was performed (p = 0.015).Conclusions: HuR cytoplasmic expression was correlated with adverse phenotypes and cyclin A overexpression and also independently predictive of worse DSS and MeFS, suggesting its roles in tumorigenesis or carcinogenesis and potentiality as a prognostic marker of UTUC. High HuR cytoplasmic expression might identify patients more likely to be beneficial for adjuvant chemotherapy.

Original languageEnglish
Article number611
JournalBMC Cancer
Volume12
DOIs
Publication statusPublished - Dec 21 2012

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Cyclin A
Urinary Tract
Carcinoma
Survival
Neoplasm Metastasis
Carcinogenesis
Urinary Bladder
Adjuvant Chemotherapy
Recurrence
RNA-Binding Proteins
Blood Vessels

Keywords

  • Cyclin A
  • HuR
  • Prognosis
  • Upper urinary tract urothelial carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Genetics

Cite this

HuR cytoplasmic expression is associated with increased cyclin A expression and poor outcome with upper urinary tract urothelial carcinoma. / Liang, Peir In; Li, Wei Ming; Wang, Yu Hui; Wu, Ting Feng; Wu, Wen Ren; Liao, Alex C.; Shen, Kun Hung; Wei, Yu Ching; Hsing, Chung-Hsi; Shiue, Yow Ling; Huang, Hsuan Ying; Hsu, Han Ping; Chen, Li Tzong; Lin, Ching Yih; Tai, Chein; Lin, Chun-Mao; Li, Chien Feng.

In: BMC Cancer, Vol. 12, 611, 21.12.2012.

Research output: Contribution to journalArticle

Liang, PI, Li, WM, Wang, YH, Wu, TF, Wu, WR, Liao, AC, Shen, KH, Wei, YC, Hsing, C-H, Shiue, YL, Huang, HY, Hsu, HP, Chen, LT, Lin, CY, Tai, C, Lin, C-M & Li, CF 2012, 'HuR cytoplasmic expression is associated with increased cyclin A expression and poor outcome with upper urinary tract urothelial carcinoma', BMC Cancer, vol. 12, 611. https://doi.org/10.1186/1471-2407-12-611
Liang, Peir In ; Li, Wei Ming ; Wang, Yu Hui ; Wu, Ting Feng ; Wu, Wen Ren ; Liao, Alex C. ; Shen, Kun Hung ; Wei, Yu Ching ; Hsing, Chung-Hsi ; Shiue, Yow Ling ; Huang, Hsuan Ying ; Hsu, Han Ping ; Chen, Li Tzong ; Lin, Ching Yih ; Tai, Chein ; Lin, Chun-Mao ; Li, Chien Feng. / HuR cytoplasmic expression is associated with increased cyclin A expression and poor outcome with upper urinary tract urothelial carcinoma. In: BMC Cancer. 2012 ; Vol. 12.
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title = "HuR cytoplasmic expression is associated with increased cyclin A expression and poor outcome with upper urinary tract urothelial carcinoma",
abstract = "Background: HuR is an RNA-binding protein that post-transcriptionally modulates the expressions of various target genes implicated in carcinogenesis, such as CCNA2 encoding cyclin A. No prior study attempted to evaluate the significance of HuR expression in a large cohort with upper urinary tract urothelial carcinomas (UTUCs).Methods: In total, 340 cases of primary localized UTUC without previous or concordant bladder carcinoma were selected. All of these patients received ureterectomy or radical nephroureterectomy with curative intents. Pathological slides were reviewed, and clinical findings were collected. Immunostaining for HuR and cyclin A was performed and evaluated by using H-score. The results of cytoplasmic HuR and nuclear cyclin A expressions were correlated with disease-specific survival (DSS), metastasis-free survival (MeFS), urinary bladder recurrence-free survival (UBRFS), and various clinicopathological factors.Results: HuR cytoplasmic expression was significantly related to the pT status, lymph node metastasis, a higher histological grade, the pattern of invasion, vascular and perineurial invasion, and cyclin A expression (p = 0.005). Importantly, HuR cytoplasmic expression was strongly associated with a worse DSS (p <0.0001), MeFS (p <0.0001), and UBRFS (p = 0.0370) in the univariate analysis, and the first two results remained independently predictive of adverse outcomes (p = 0.038, relative risk [RR] = 1.996 for DSS; p = 0.027, RR = 1.880 for MeFS). Cyclin A nuclear expression was associated with a poor DSS (p = 0.0035) and MeFS (p = 0.0015) in the univariate analysis but was not prognosticatory in the multivariate analyses. High-risk patients (pT3 or pT4 with/without nodal metastasis) with high HuR cytoplasmic expression had better DSS if adjuvant chemotherapy was performed (p = 0.015).Conclusions: HuR cytoplasmic expression was correlated with adverse phenotypes and cyclin A overexpression and also independently predictive of worse DSS and MeFS, suggesting its roles in tumorigenesis or carcinogenesis and potentiality as a prognostic marker of UTUC. High HuR cytoplasmic expression might identify patients more likely to be beneficial for adjuvant chemotherapy.",
keywords = "Cyclin A, HuR, Prognosis, Upper urinary tract urothelial carcinoma",
author = "Liang, {Peir In} and Li, {Wei Ming} and Wang, {Yu Hui} and Wu, {Ting Feng} and Wu, {Wen Ren} and Liao, {Alex C.} and Shen, {Kun Hung} and Wei, {Yu Ching} and Chung-Hsi Hsing and Shiue, {Yow Ling} and Huang, {Hsuan Ying} and Hsu, {Han Ping} and Chen, {Li Tzong} and Lin, {Ching Yih} and Chein Tai and Chun-Mao Lin and Li, {Chien Feng}",
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language = "English",
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journal = "BMC Cancer",
issn = "1471-2407",
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TY - JOUR

T1 - HuR cytoplasmic expression is associated with increased cyclin A expression and poor outcome with upper urinary tract urothelial carcinoma

AU - Liang, Peir In

AU - Li, Wei Ming

AU - Wang, Yu Hui

AU - Wu, Ting Feng

AU - Wu, Wen Ren

AU - Liao, Alex C.

AU - Shen, Kun Hung

AU - Wei, Yu Ching

AU - Hsing, Chung-Hsi

AU - Shiue, Yow Ling

AU - Huang, Hsuan Ying

AU - Hsu, Han Ping

AU - Chen, Li Tzong

AU - Lin, Ching Yih

AU - Tai, Chein

AU - Lin, Chun-Mao

AU - Li, Chien Feng

PY - 2012/12/21

Y1 - 2012/12/21

N2 - Background: HuR is an RNA-binding protein that post-transcriptionally modulates the expressions of various target genes implicated in carcinogenesis, such as CCNA2 encoding cyclin A. No prior study attempted to evaluate the significance of HuR expression in a large cohort with upper urinary tract urothelial carcinomas (UTUCs).Methods: In total, 340 cases of primary localized UTUC without previous or concordant bladder carcinoma were selected. All of these patients received ureterectomy or radical nephroureterectomy with curative intents. Pathological slides were reviewed, and clinical findings were collected. Immunostaining for HuR and cyclin A was performed and evaluated by using H-score. The results of cytoplasmic HuR and nuclear cyclin A expressions were correlated with disease-specific survival (DSS), metastasis-free survival (MeFS), urinary bladder recurrence-free survival (UBRFS), and various clinicopathological factors.Results: HuR cytoplasmic expression was significantly related to the pT status, lymph node metastasis, a higher histological grade, the pattern of invasion, vascular and perineurial invasion, and cyclin A expression (p = 0.005). Importantly, HuR cytoplasmic expression was strongly associated with a worse DSS (p <0.0001), MeFS (p <0.0001), and UBRFS (p = 0.0370) in the univariate analysis, and the first two results remained independently predictive of adverse outcomes (p = 0.038, relative risk [RR] = 1.996 for DSS; p = 0.027, RR = 1.880 for MeFS). Cyclin A nuclear expression was associated with a poor DSS (p = 0.0035) and MeFS (p = 0.0015) in the univariate analysis but was not prognosticatory in the multivariate analyses. High-risk patients (pT3 or pT4 with/without nodal metastasis) with high HuR cytoplasmic expression had better DSS if adjuvant chemotherapy was performed (p = 0.015).Conclusions: HuR cytoplasmic expression was correlated with adverse phenotypes and cyclin A overexpression and also independently predictive of worse DSS and MeFS, suggesting its roles in tumorigenesis or carcinogenesis and potentiality as a prognostic marker of UTUC. High HuR cytoplasmic expression might identify patients more likely to be beneficial for adjuvant chemotherapy.

AB - Background: HuR is an RNA-binding protein that post-transcriptionally modulates the expressions of various target genes implicated in carcinogenesis, such as CCNA2 encoding cyclin A. No prior study attempted to evaluate the significance of HuR expression in a large cohort with upper urinary tract urothelial carcinomas (UTUCs).Methods: In total, 340 cases of primary localized UTUC without previous or concordant bladder carcinoma were selected. All of these patients received ureterectomy or radical nephroureterectomy with curative intents. Pathological slides were reviewed, and clinical findings were collected. Immunostaining for HuR and cyclin A was performed and evaluated by using H-score. The results of cytoplasmic HuR and nuclear cyclin A expressions were correlated with disease-specific survival (DSS), metastasis-free survival (MeFS), urinary bladder recurrence-free survival (UBRFS), and various clinicopathological factors.Results: HuR cytoplasmic expression was significantly related to the pT status, lymph node metastasis, a higher histological grade, the pattern of invasion, vascular and perineurial invasion, and cyclin A expression (p = 0.005). Importantly, HuR cytoplasmic expression was strongly associated with a worse DSS (p <0.0001), MeFS (p <0.0001), and UBRFS (p = 0.0370) in the univariate analysis, and the first two results remained independently predictive of adverse outcomes (p = 0.038, relative risk [RR] = 1.996 for DSS; p = 0.027, RR = 1.880 for MeFS). Cyclin A nuclear expression was associated with a poor DSS (p = 0.0035) and MeFS (p = 0.0015) in the univariate analysis but was not prognosticatory in the multivariate analyses. High-risk patients (pT3 or pT4 with/without nodal metastasis) with high HuR cytoplasmic expression had better DSS if adjuvant chemotherapy was performed (p = 0.015).Conclusions: HuR cytoplasmic expression was correlated with adverse phenotypes and cyclin A overexpression and also independently predictive of worse DSS and MeFS, suggesting its roles in tumorigenesis or carcinogenesis and potentiality as a prognostic marker of UTUC. High HuR cytoplasmic expression might identify patients more likely to be beneficial for adjuvant chemotherapy.

KW - Cyclin A

KW - HuR

KW - Prognosis

KW - Upper urinary tract urothelial carcinoma

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U2 - 10.1186/1471-2407-12-611

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