IGFBP-5 overexpression as a poor prognostic factor in patients with urothelial carcinomas of upper urinary tracts and urinary bladder

Liang, Peir‐In; Wang, Yu Hui; Wu, Ting; Wu, Wen Jeng; Liao, Alex Chien-Hwa; Shen, Kun Hung; Hsing, Chung-Hsi; Shiue, Yow Ling; Huang, Hsuan Ying; Hsu, Han Ping; Chen, Li Tzon; Lin, Ching Yih; Tai, Cheng‐Chi; Wu, Jui Yu; Li, Chien‐Feng

doi:10.1136/jclinpath-2012-201278

Cited by 44 publications

(37 citation statements)

References 29 publications

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“…Circulating concentrations of insulin-like growth factor (IGF) and certain insulin-like growth factor binding proteins (IGFBP) are associated with higher risk and worse outcome among patients with bladder, as well as colorectal, prostate and breast cancers (41). Thus, it is possible that patients with worse glycemic control had lower levels of insulin in the serum and thus improved prognosis.…”

Section: Discussionmentioning

confidence: 99%

Serum glucose and hemoglobin A1C levels at cancer diagnosis and disease outcome

Boursi

Giantonio

Haynes

et al. 2016

European Journal of Cancer

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Background Despite the lack of scientific data, many cancer patients hold the belief that glucose “feeds” cancer and might affect disease outcome. We aimed to evaluate associations between glucose, hemoglobin A1C (HbA1C), and survival among individuals with diabetes and diabetes associated cancers. Methods Five retrospective cohort studies were conducted in a large population-representative database. The study population included all patients with diabetes and an incident diagnosis of colorectal, breast, bladder, pancreatic and prostate cancers. Exposure of interest was serum glucose or HbA1C levels within 6 months prior to cancer diagnosis. Cox regression model was used to calculate hazard-ratio (HR) and 95% confidence-interval (CI) for overall survival. Analyses were adjusted for cancer-specific confounders. A subgroup analysis was performed among insulin-treated patients. Results Study cohorts included 7,916 individuals with incident cancers and concurrent diabetes. There was no association between HbA1C levels and overall survival in colorectal (HR 1.00, 95%CI 0.95-1.06), breast (HR 1.03, 95%CI 0.95-1.11), bladder (HR 0.94, 95%CI 0.86-1.01), pancreatic (HR 0.98, 95%CI 0.94-1.02), or prostate (HR 1.02, 95%CI 0.96-1.08) cancers. Among diabetes patients treated with insulin, there was increased survival with increasing serum glucose, most prominent for bladder cancer (HRs 0.91, 95%CI 0.84-0.99, per 1 mmol/L increase). Conclusions Higher glucose and HbA1C levels in diabetes patients with incident cancer are not associated with worse overall survival following cancer diagnosis. Among insulin-treated patients, higher glucose levels may be associated with improved survival.

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Section: Discussionmentioning

confidence: 99%

Serum glucose and hemoglobin A1C levels at cancer diagnosis and disease outcome

Boursi

Giantonio

Haynes

et al. 2016

European Journal of Cancer

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“…In comparison, only 29 of the 106 UTUC patients with pT3 or pT4 stage and/or nodal involvement received adjuvant chemotherapy. The criteria for the clinicopathological evaluation were essentially identical to our previous studies 23-28.…”

Section: Methodsmentioning

confidence: 99%

“…In this formula, i represents the intensity of the stained tumor cells (0-3+), and Pi is the percentage of stained tumor cells for each intensity varying from 0% to 100%, with an obtained score ranging from 100-400. The score 100 indicated that 100% of tumor cells were negative, and 400 indicated that 100% of tumor cells showed an intense, strong staining (3+) 23-28. Concordance for interpretation of RNF128 between the two pathologists was above 90%.…”

Section: Methodsmentioning

confidence: 99%

Downregulation of RNF128 Predicts Progression and Poor Prognosis in Patients with Urothelial Carcinoma of the Upper Tract and Urinary Bladder

Lee¹,

Wang²,

Huang³

et al. 2016

J. Cancer

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Background: The TP53 tumor suppressor gene plays a crucial role in the carcinogenesis of many malignancies, including urothelial carcinoma (UC). Overexpression of p53 is associated with poor prognosis in UC. Recently, RING finger protein 128 (RNF128) was shown to be involved in p53-induced apoptosis, forming a negative feedback loop. However, the significance of RNF128 in patients with UC remains unknown. In this study, our aim was to evaluate the expression of RNF128 in UC and to assess its predictive and prognostic value in a well-established cohort.Methods: Through data mining from a published transcriptome (GSE31684), RNF128 was identified as the most differentially expressed gene in UC among those associated with negative regulation of the cytokine biosynthetic process (GO:0042036). Its immunoexpression was further evaluated using the H-scores of 340 patients with upper urinary tract UC (UTUC) and 295 with urinary bladder UC (UBUC). The scores were correlated with clinicopathological features, disease-specific survival (DSS) and metastasis-free survival (MeFS). We also used Western blot analysis to evaluate RNF128 protein expression in human urothelial cell (HUC) lines.Results: Downregulation of RNF128 expression was significantly associated with advanced pT stage (p<0.001), high histological grade (UTUC, p<0.001; UBUC, p=0.035), nodal metastasis (UTUC, p<0.001; UBUC, p=0.001), vascular invasion (UTUC, p<0.001; UBUC, p=0.008) and high mitotic rate (UTUC, p=0.003; UBUC, p=0.023). Low expression of RNF128 was an adverse prognosticator for DSS (UTUC, p<0.0001; UBUC, p<0.0001) and MeFS (UTUC, p<0.0001; UBUC, p=0.0002). Moreover, low expression was predictive of poor DSS (UTUC, p=0.006; UBUC, p=0.003) and MeFS (UTUC, p=0.009; UBUC, p=0.036) in multivariate comparisons. Western blot analysis showed that the RNF128 protein was downregulated in invasive urothelial cancer cell lines.Conclusion: Our findings showed that downregulation of RNF128 was correlated with cancer invasiveness and metastasis as well as reduced survival in patients with UTUC and UBUC, identifying RNF128 as a prognostic factor in UC.

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“…Numerous studies investigated the prognostic impact of various tissue-based molecular markers that are related to cellular processes such as cell adhesion (Metalloproteinase-9, E-cadherin [33], ParvB [34], snail [35], b-catenin[36]), cell signaling (EGFR[37], EMP3 [38], HER2 [4], PI3K/AKT [39, 40], IGFBP-5 [41], mTOR [42]), angiogenesis (Hypoxia-inducible factor-1[43]), cell proliferation (Ki67[44], p27 [45],cyclin D[46], NF- κ B [47], Aurora-A[48]), cell transport (GRP78 [49]) and apoptosis (bcl-2, survivin [50]). Recently, Wu et al compared the genome-wide mRNA expression profile using digital gene expression sequencing of tumors and matched normal tissues in 10 UTUC patients.…”

Section: Potential Biomarkers From Gene Expression Profilingmentioning

confidence: 99%

Prognostic Genetic Signatures in Upper Tract Urothelial Carcinoma

Bagrodia

Eugene

2016

Curr Urol Rep

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Urothelial carcinoma is a highly heterogeneous disease that can arise throughout the entire urothelial lining from the renal pelvis to the proximal urethra. Upper tract urothelial carcinoma (UTUC) is rare and while it shares many similarities with urothelial carcinoma of bladder (UCB), there are also significant differences between UTUC and UCB regarding clinical management and outcomes. No major advances have been made recently in the development of new systemic therapies for urothelial carcinoma, partly due to the lack of understanding of underlying molecular pathogenetic mechanisms. In the past decade, the emergence of next-generation sequencing has greatly enabled genomic characterization of tumor samples. Researchers are currently exploring a personalized approach to augment traditional clinical decision-making based on genetic alterations. In the present review, we summarize current genomic advances in UTUC and discuss the potential implications of these developments for developing prognostic and predictive biomarkers.

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IGFBP-5 overexpression as a poor prognostic factor in patients with urothelial carcinomas of upper urinary tracts and urinary bladder

Abstract: IGFBP-5 plays an important role in tumour progression in UC. Its overexpression is associated with advanced tumour stage and conferred poorer clinical outcome.

Cited by 44 publications

References 29 publications

Serum glucose and hemoglobin A1C levels at cancer diagnosis and disease outcome

Serum glucose and hemoglobin A1C levels at cancer diagnosis and disease outcome

Downregulation of RNF128 Predicts Progression and Poor Prognosis in Patients with Urothelial Carcinoma of the Upper Tract and Urinary Bladder

Prognostic Genetic Signatures in Upper Tract Urothelial Carcinoma

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