Significance of S100A8, S100A9 and calprotectin levels in bladder cancer

Yasar, Ozgur; Akçay, Tülay; Öbek, Can; Türegün, Fethi Ahmet

doi:10.1080/00365513.2017.1336567

Cited by 33 publications

(28 citation statements)

References 21 publications

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“…Features overexpressed consistently in the aggressive NMIBC phenotypes represented predominantly inflammation and immune recognition, unfolded protein response, oncogenic signaling and RNA processing. The former observations are in line to previous findings at the protein level, supporting an increase in the abundance levels of damage associated features (such as S100A8/A9 and HMGB2), with BC stage, 46,47 and enhance previous findings of the Lund taxonomy associating high mRNA levels of antigen presentation molecules with the most aggressive BC subtypes. 3 Of note, high levels of STAT1, EIF4A3 and EIF4G1 which are potentially controlling PD-L1 regulation based on evidence from melanoma, 48 were detected in NPS1.…”

Section: Discussionsupporting

confidence: 91%

Proteome‐based classification of Nonmuscle Invasive Bladder Cancer

Stroggilos

Mokou

Latosinska

et al. 2019

Intl Journal of Cancer

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DNA/RNA‐based classification of bladder cancer (BC) supports the existence of multiple molecular subtypes, while investigations at the protein level are scarce. Here, we aimed to investigate if Nonmuscle Invasive Bladder Cancer (NMIBC) can be stratified to biologically meaningful groups based on the proteome. Tissue specimens from 117 patients at primary diagnosis (98 with NMIBC and 19 with MIBC), were processed for high‐resolution proteomics analysis by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). The proteomics output was subjected to unsupervised consensus clustering, principal component analysis (PCA) and investigation of subtype‐specific features, pathways, and gene sets. NMIBC patients were optimally stratified to three NMIBC proteomic subtypes (NPS), differing in size, clinicopathologic and molecular backgrounds: NPS1 (mostly high stage/grade/risk samples) was the smallest in size (17/98) and overexpressed proteins reflective of an immune/inflammatory phenotype, involved in cell proliferation, unfolded protein response and DNA damage response, whereas NPS2 (mixed stage/grade/risk composition) presented with an infiltrated/mesenchymal profile. NPS3 was rich in luminal/differentiation markers, in line with its pathological composition (mostly low stage/grade/risk samples). PCA revealed a close proximity of NPS1 and conversely, remoteness of NPS3 to the proteome of MIBC. Proteins distinguishing these two extreme subtypes were also found to consistently differ at the mRNA levels between high and low‐risk subtypes of the UROMOL and LUND cohorts. Collectively, our study identifies three proteomic NMIBC subtypes and following a cross‐omics validation in two independent cohorts, shortlists molecular features meriting further investigation for their biomarker or potentially therapeutic value.

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Section: Discussionsupporting

confidence: 91%

Proteome‐based classification of Nonmuscle Invasive Bladder Cancer

Stroggilos

Mokou

Latosinska

et al. 2019

Intl Journal of Cancer

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“…Calprotectin has been studied as a biomarker for several different diseases, and its main current use in the assessment of inflammatory bowel diseases by analysing faeces 21 . However, calprotectin has been studied as a diagnostic marker in urine for the diagnosis and staging of bladder cancer 22 . We were only able to identify one study that used calprotectin as a marker in PE to analyse the efficacy and diagnostic accuracy of a combination of calprotectin and CXCL12 23 .…”

Section: Discussionmentioning

confidence: 99%

Validation of Calprotectin As a Novel Biomarker For The Diagnosis of Pleural Effusion: a Multicentre Trial

Botana-Rial

Vázquez-Iglesias

Casado-Rey

et al. 2020

Sci Rep

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Discriminating between malignant pleural effusion (MPE) and benign pleural effusion (BPE) remains difficult. Thus, novel and efficient biomarkers are required for the diagnosis of pleural effusion (PE). The aim of this study was to validate calprotectin as a diagnostic biomarker of PE in clinical settings. A total of 425 patients were recruited, and the pleural fluid samples collected had BPE in 223 cases (53.7%) or MPE in 137 patients (33%). The samples were all analysed following the same previously validated clinical laboratory protocols and methodology. Calprotectin levels ranged from 772.48 to 3,163.8 ng/mL (median: 1,939 ng/mL) in MPE, and 3,216-24,000 ng/mL in BPE (median: 9,209 ng/mL; p < 0.01), with an area under the curve of 0.848 [95% CI: 0.810-0.886]. For a cutoff value of ≤ 6,233.2 ng/mL, we found 96% sensitivity and 60% specificity, with a negative and positive predictive value, and negative and positive likelihood ratios of 96%, 57%, 0.06, and 2.4, respectively. Multivariate analysis showed that low calprotectin levels was a better discriminator of PE than any other variable [OR 28.76 (p < 0.0001)]. Our results confirm that calprotectin is a new and useful diagnostic biomarker in patients with PE of uncertain aetiology which has potential applications in clinical practice because it may be a good complement to cytological methods. The diagnosis of pleural effusion (PE) is a clinical challenge because it can be produced by over 60 diseases 1,2. Nevertheless, in clinical practice the priority is to establish whether the PE is malignant or not. A diagnosis of malignant PE (MPE) implies the presence of advanced-stage tumours and is therefore associated with a poor prognosis 1,3 which requires urgent diagnosis. Thoracocentesis is the first and most simple procedure for the diagnosis of PE 2-4. Unfortunately, while its specificity for establishing malignancy is 100%, the diagnostic sensitivity of pleural fluid (PF) cytological analysis is low. Although the odds of establishing an MPE diagnosis by immunohistochemistry are improved by applying a panel of different antibodies, its diagnostic sensitivity is still only approximately 60% for metastatic PE and less than 30% for mesothelioma 5,6. When the cytology results are negative, more invasive methods such as a pleural biopsy or thoracoscopy are necessary 2,4,7. In this context, more groups are searching for PF biomarkers for malignancy with the aim of avoiding these invasive procedures 8-10. Recent meta-analyses have evaluated the ability of new biomarkers such

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“…The one exception is the study of calprotectin, where Yasar et al compared 82 cases that did not receive any prior treatment with 52 healthy controls, and reported 81% sensitivity at 84% specificity and an AUC of 0.9. Diagnostic accuracy of calprotectin was compared to the one of Bladder Tumor Antigen (BTA) tests, which reached 89% sensitivity, 88% specificity and an AUC of 0.95 on the same group of patients [11]. When compared with earlier publications, these results for BTA are unusually good, which further questions the high diagnostic accuracy of calprotectin [4].…”

Section: Casementioning

confidence: 91%

The significance of calprotectin, CD147, APOA4 and DJ-1 in non-invasive detection of urinary bladder carcinoma

Soukup¹,

Čapoun²,

Pešl³

et al. 2019

neo

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Aim of the study is to define the diagnostic accuracy of selected urinary protein biomarkers in the non-invasive detection of primary and recurrent urothelial carcinoma of the urinary bladder. The urinary levels of calprotectin, CD147, APOA4 and protein deglycase DJ-1 were examined in 255 individuals, including 60 controls with non-malignant urological disease, 61 patients with a history of urinary bladder cancer with negative cytology and negative cystoscopy and 134 patients with urinary bladder cancer. Urinary concentrations of biomarkers were determined by Enzyme-Linked Immunosorbent Assay (ELISA). During the follow-up of patients with non-muscle invasive bladder cancer (NMIBC), a group of 44 patients with cancer recurrence was compared to the group of 61 patients with a history of NMIBC but with no evidence of disease. Urinary concentrations of the evaluated markers did not reveal any significant difference between these groups. During the primary diagnosis, a group of 90 patients with primary bladder cancer and 60 subjects with benign disease were compared. Urinary levels of CD147 were not significantly higher in patients with tumors. The greatest diagnostic accuracy was observed in APOA4 (sensitivity 55.6, specificity 83.3, AUC 0.75), and lesser in calprotectin (sensitivity 39.4, specificity 87.7, AUC 0.66) and in DJ-1 (sensitivity 61.1, specificity 66.7, AUC 0.64), respectively. Apolipoprotein A4 may be used potentially as a supplemental urinary marker in the diagnosis of primary bladder cancer.

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Significance of S100A8, S100A9 and calprotectin levels in bladder cancer

Abstract: Urine calprotectin levels can be used in the diagnosis and staging of bladder cancer as a marker for muscle invasion.

Cited by 33 publications

References 21 publications

Proteome‐based classification of Nonmuscle Invasive Bladder Cancer

Proteome‐based classification of Nonmuscle Invasive Bladder Cancer

Validation of Calprotectin As a Novel Biomarker For The Diagnosis of Pleural Effusion: a Multicentre Trial

The significance of calprotectin, CD147, APOA4 and DJ-1 in non-invasive detection of urinary bladder carcinoma

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