Dataset Information

A panel of tumor markers, calreticulin, annexin A2, and annexin A3 in upper tract urothelial carcinoma identified by proteomic and immunological analysis.

ABSTRACT: BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a tumor with sizable metastases and local recurrence. It has a worse prognosis than bladder cancer. This study was designed to investigate the urinary potential tumor markers of UTUC. METHODS: Between January 2008 and January 2009, urine was sampled from 13 patients with UTUC and 20 healthy adults. The current study identified biomarkers for UTUC using non-fixed volume stepwise weak anion exchange chromatography for fractionation of urine protein prior to two-dimensional gel electrophoresis. RESULTS: Fifty five differential proteins have been determined by comparing with the 2-DE maps of the urine of UTUC patients and those of healthy people. Western blotting analysis and immunohistochemistry of tumor tissues and normal tissues from patients with UTUC were carried out to further verify five possible UTUC biomarkers, including zinc-alpha-2-glycoprotein, calreticulin, annexin A2, annexin A3 and haptoglobin. The data of western blot and immunohistochemical analysis are consistent with the 2-DE data. Combined the experimental data in the urine and in tumor tissues collected from patients with UTUC, the crucial over-expressed proteins are calreticulin, annexin A2, and annexin A3. CONCLUSIONS: Calreticulin, annexin A2, and annexin A3 are very likely a panel of biomarkers with potential value for UTUC diagnosis.

SUBMITTER: Lu CM

PROVIDER: S-EPMC4039341 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A panel of tumor markers, calreticulin, annexin A2, and annexin A3 in upper tract urothelial carcinoma identified by proteomic and immunological analysis.

Lu Chih-Ming CM Lin Jen-Jie JJ Huang Han-Hsiang HH Ko Ying-Chin YC Hsu Jue-Liang JL Chen Jiing-Chuan JC Din Zhong-Hao ZH Wu Yu-Jen YJ

BMC cancer 20140523

<h4>Background</h4>Upper tract urothelial carcinoma (UTUC) is a tumor with sizable metastases and local recurrence. It has a worse prognosis than bladder cancer. This study was designed to investigate the urinary potential tumor markers of UTUC.<h4>Methods</h4>Between January 2008 and January 2009, urine was sampled from 13 patients with UTUC and 20 healthy adults. The current study identified biomarkers for UTUC using non-fixed volume stepwise weak anion exchange chromatography for fractionatio ...[more]

PMID: 24884814

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Project description:Despite a similar histologic appearance, upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) tumors have distinct epidemiologic and clinicopathologic differences.To investigate whether the differences between UTUC and UCB result from intrinsic biological diversity.Tumor and germline DNA from patients with UTUC (n=83) and UCB (n=102) were analyzed using a custom next-generation sequencing assay to identify somatic mutations and copy number alterations in 300 cancer-associated genes.We described co-mutation patterns and copy number alterations in UTUC. We also compared mutation frequencies in high-grade UTUC (n=59) and high-grade UCB (n=102).Comparison of high-grade UTUC and UCB revealed significant differences in the prevalence of somatic alterations. Genes altered more commonly in high-grade UTUC included FGFR3 (35.6% vs 21.6%; p=0.065), HRAS (13.6% vs 1.0%; p=0.001), and CDKN2B (15.3% vs 3.9%; p=0.016). Genes less frequently mutated in high-grade UTUC included TP53 (25.4% vs 57.8%; p<0.001), RB1 (0.0% vs 18.6%; p<0.001), and ARID1A (13.6% vs 27.5%; p=0.050). Because our assay was restricted to genomic alterations in a targeted panel, rare mutations and epigenetic changes were not analyzed.High-grade UTUC tumors display a spectrum of genetic alterations similar to high-grade UCB. However, there were significant differences in the prevalence of several recurrently mutated genes including HRAS, TP53, and RB1. As relevant targeted inhibitors are being developed and tested, these results may have important implications for the site-specific management of patients with urothelial carcinoma.Comparison of next-generation sequencing of upper tract urothelial carcinoma (UTUC) with urothelial bladder cancer identified that similar mutations were present in both cancer types but at different frequencies, indicating a potential need for unique management strategies. UTUC tumors were found to have a high rate of mutations that could be targeted with novel therapies.

Project description:The aim of this study was to investigate the effect of preoperative anemia on the prognosis of patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC).A total of 620 patients with UTUC were retrospectively analyzed. Anemia was decided by preoperatively measured hemoglobin values based on the World Health Organization (WHO) classification. Kaplan-Meier method and Cox proportional hazards regression models were used to analyze the relationship between anemia and survival outcomes. The meta-analysis part was performed according to PRISMA guidelines.The median follow-up was 51 (range: 1-168) months. A total of 246 patients had preoperative anemia in our cohort. Anemia was found to be related to high-grade (P < .001), sessile architecture (P = .001), advanced T stage (P < .001), lymphovascular invasion (LVI) (P = .006), and worse chronic kidney disease (CKD) stage (P = .012). Kaplan-Meier curves revealed that patients with preoperative anemia had worse overall survival (OS), cancer-specific survival (CSS), and disease recurrence-free survival (RFS) (all P < .001). Multivariable Cox analyses found that anemia was an independent predictor of CSS [hazard ratio (HR) 1.719, 95% confidence interval (95% CI): 1.285-2.300], RFS (HR 1.427, 95% CI: 1.114-1.829) and OS (HR 1.756, 95% CI: 1.353-2.279). Among patients without end-stage renal disease (ESRD, n = 614), the anemia was also proved to be associated with worse outcomes in multivariable Cox analysis (OS, HR 1.759, 95% CI: 1.353-2.287; CSS, HR 1.726, 95% CI: 1.289-2.311, and RFS, HR 1.431, 95% CI: 1.117-1.837). Seven studies were included in the meta-analysis, and the pooled results showed that anemia was also related to worse CSS (HR 2.05, 95% CI: 1.73-2.44), RFS (HR 1.57, 95% CI: 1.30-1.90), and OS (HR 1.53, 95% CI: 1.10-2.13), but not related to intravesical recurrence (HR 1.17, 95% CI: 0.75-1.82).Preoperative anemia was proved to be significantly associated with worse oncologic outcomes in patients with UTUC following RNU.

Project description:BackgroundDifferent genomic characterization in urothelial carcinoma (UC) by site of origin may imply contrasting therapeutic opportunities and pathogenetic mechanisms. The aim of this study was to investigate whether differences between upper tract UC (UTUC) and UC of the bladder (UCB) result from intrinsic biological diversity.Materials and methodsWe prospectively sequenced 118 tumors and matched blood DNA from Chinese patients with UC using next-generation sequencing techniques, including 45 UTUC and 73 UCB. Two hundred twenty-six patients with UTUC and 350 patients with UCB for The Cancer Genome Atlas were acquired from the cbioportal.ResultsThere were marked disparities in the mutational landscape for UC according to race and site of origin. Signature 22 for exposure to aristolochic acid was only observed in the UTUC cohort. Conversely, signature 6 for defective DNA mismatch repair only existed in the UCB cohort. Compared with UCB, UTUC had higher clonal and subclonal mutation numbers. TP53, PIK3CA, and FGFR3 mutations may be the driver genes for UTUC, whereas for UCB, the driver gene may be BRCA1. Patients with UTUC had lower PD-L1 than those with UCB. There was no significant difference in the number of DDR mutations, copy number variation counts, and tumor mutational burden between UTUC and UCB.ConclusionUTUC and UCB exhibit significant differences in the prevalence of genomic landscape and carcinogenesis. Consequently, molecular subtypes differ according to location, and these results may imply the site-specific management of patients with urothelial carcinoma. Mutational signature may be used as a screening tool to assist clinical differential diagnosis between UTUC and UCB.Implications for practiceThis study's findings lay the foundation for a deeper understanding of distinct molecular mechanisms and similar treatment opportunities between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) and had important implications for the site-specific management of patients with urothelial carcinoma. A comprehensive understanding of the biology of UTUC and UCB is needed to identify new drug targets in order to improve clinical outcomes.

Dataset Information

A panel of tumor markers, calreticulin, annexin A2, and annexin A3 in upper tract urothelial carcinoma identified by proteomic and immunological analysis.

Publications

A panel of tumor markers, calreticulin, annexin A2, and annexin A3 in upper tract urothelial carcinoma identified by proteomic and immunological analysis.

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