Urinary KIM-1 and AQP-1 in patients with clear renal cell carcinoma: Potential noninvasive biomarkers

Mijugkovic, Mirjana; Stanojević, Ivan; Novák, Miroslav; Cerović, Snežana; Petrović, Dejan; Jovanović, D; Aleksić, Predrag; Kovačević, Božidar; Andjelic, Tamara; Terzić, Brankica; Djukić, Mirjana; Vojvodić, Danilo

doi:10.2298/vsp150124006m

Cited by 5 publications

(7 citation statements)

References 25 publications

(30 reference statements)

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“…Despite only evaluating exosomal AQP1 concentrations, their results corroborated previous studies showing AQP1 is downregulated in RCC tissues and has a significant negative correlation with an unfavourable outcome [60,61]. Mijuskovic et al [36] reported that uAQP1 is twofold lower in patients with RCC than healthy volunteers (P = 0.001), and concentrations increased after nephrectomy. The group also stated no significant correlations between uAQP1 levels and prognostic factors.…”

Section: Aquaporin-1supporting

confidence: 77%

“…Seemingly, there are discrepancies in the link between uAQP1 and ccRCC/pRCC presence between external laboratory findings (Table 2). Regardless of the considerably lower study numbers reported by Mijuskovic et al [36] and Raimondo et al [7] compared to the extensive studies carried out by Morrissey et al…”

Section: Aquaporin-1mentioning

confidence: 85%

“…Despite the vast work carried out by Morrissey et al [30,31,[33][34][35], confirmation in independent cohorts, and prospective identification of patients (Table 1), numerous external studies show that uAQP1 and tissue AQP1 concentrations are decreased in patients with RCC compared to healthy controls [7,32,36,60,61]. Raimondo et al [7] reported a fourfold decrease in RCC patients' AQP1 urinary exosome concentrations compared to matched healthy controls.…”

Section: Aquaporin-1mentioning

confidence: 99%

“…In disease states, the extracellular domain of KIM-1 is shed into the urine and serves as a sensitive urinary marker for proximal tubule injury. Elevated urinary KIM-1 (uKIM-1) levels, ranging from twofold to >30-fold, have been strongly correlated with increased risk of RCC as well as tumour size and stage [36,[45][46][47]. However, more evaluation is necessary as conflicting evidence has been found, particularly in cohorts consisting of patients with other renal conditions [48].…”

Section: Kidney Injury Molecule-1mentioning

confidence: 99%

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Early detection of kidney cancer using urinary proteins: a truly non‐invasive strategy

et al. 2021

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To review urinary protein biomarkers as potential non-invasive, easily obtainable, early diagnostic tools in renal cell carcinoma (RCC). MethodsA PubMed database search was performed up to the year 2020 to identify primary studies reporting potential urinary protein biomarkers for RCC. Separate searches were conducted to identify studies describing appropriate methods of developing cancer screening programmes and detection of cancer biomarkers. ResultsSeveral urinary protein biomarkers are under validation for RCC diagnostics, e.g. aquaporin-1, perilipin-2, carbonic anhydrase-9, Raf-kinase inhibitory protein, nuclear matrix protein-22, 14-3-3 Protein b/a and neutrophil gelatinaseassociated lipocalin. However, none has yet been validated or approved for clinical use due to low sensitivity or specificity, inconsistencies in appropriate study design, or lack of external validation. ConclusionsEvaluation of biomarkers' feasibility, sample preparation and storage, biomarker validation, and the application of novel technologies may provide a solution that maximises the potential for a truly non-invasive biomarker in early RCC diagnostics.

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Section: Aquaporin-1supporting

confidence: 77%

Section: Aquaporin-1mentioning

confidence: 85%

Section: Aquaporin-1mentioning

confidence: 99%

Section: Kidney Injury Molecule-1mentioning

confidence: 99%

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Early detection of kidney cancer using urinary proteins: a truly non‐invasive strategy

et al. 2021

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“…Впоследствии эти наблюдения были подтверждены результатами исследований других авторов [10][11][12][13][14][15]. В ряде публикаций представлены данные, свидетельствующие о том, что при светлоклеточной карциноме почки уровень этого маркера в моче больных достоверно превышает таковой у здоровых лиц, а повышение концентрации KIM-1 в моче коррелирует со стадией заболевания, размером и степенью дифференцировки опухоли [12,13,15]. Содержание KIM-1 в моче больных ПКР снижается после радикальной нефрэктомии [9,12,16].…”

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KIM-1 (kidney injury molecule 1) in the urine of renal cell carcinoma patients

et al. 2020

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Objective: to assess the potential clinical significance of KIM-1 (kidney injury molecule 1) as a urinological marker for kidney cancer.Materials and methods. An enzyme-linked immunosorbent assay was used to assess urinary KIM-1 (uKIM-1 — kidney injury molecule 1) levels in 67 patients with renal cell carcinoma (RCC) and 36 healthy volunteers (a control group).Results. Both in patients and in healthy individuals, uKIM-1 levels were age independent. A difference between mean uKIM-1 values in RCC patients (2.4 ± 0.2 ng/ml) and the control group (0.7 ± 0.1 ng/ml) was statistically significant (p <0.0001). In RCC patients the higher uKIM-1 level was observed at more advanced clinical disease stages: the values increasedfrom 2.0 ± 0.2 ng/ml at the stage I and 3.0 ± 0.5 ng/ml at the stage II—III to 4.4 ± 1.2 ng/ml at the stage IV. In the group of patients with stage IRCC, most representative by the number of cases (n = 44) the uKIM-1 levels correlated with the tumor size and were increased in patients with different histological subtypes of the tumor, including clear cell, papillary and chromophobe RCC. After nephrectomy, a monotonous decrease in uKIM-1 level was observed, and after 6 days its values approached the mean value in the control group. Two days after kidney resection, uKIM-1 increased and then decreased, remaining elevated after 6 days.Conclusion. This study demonstrates that uKIM-1 can be attributed to potentially significant urine tumor-associated markers of RCC.

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Overexpression of aquaporin-1 plays a vital role in proliferation, apoptosis, and pyroptosis of Wilms’ tumor cells

Liu,

Jin,

Xia

et al. 2024

J Cancer Res Clin Oncol

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Background Nephroblastoma, also known as Wilms’ tumor (WT), is an embryonic malignant tumor and one of the most common malignant tumors in the abdominal region of children. The exact role and underlying mechanisms of aquaporin-1 (AQP1) in the occurrence and development of nephroblastoma remain unclear. Methods After overexpression of AQP1, cell proliferation was assessed using the CCK-8 proliferation assay and EdU staining. Flow cytometry was employed to assess cell apoptosis, and Western blotting (WB) analysis was conducted to validate the expression of relevant protein markers. mRNA sequencing (mRNA-Seq) was performed on WT cells overexpressing AQP1 to predict and characterize the associated mechanisms. Transmission electron microscopy was utilized to observe changes in the ultrastructure of WT cells undergoing apoptosis and pyroptosis following AQP1 overexpression. Functional in vivo validation was conducted through animal experiments. Results We validated that overexpression of AQP1 inhibited cell proliferation and promoted cell apoptosis and pyroptosis both in vitro and in vivo. mRNA-Seq analysis of WT cells with AQP1 overexpression suggested that these effects might be mediated through the inhibition of the JAK-STAT signaling pathway. Additionally, we discovered that overexpression of AQP1 activated the classical pyroptosis signaling pathway dependent on caspase-1, thereby promoting pyroptosis in WT. Conclusion These findings highlight the important functional role of AQP1 in the pathobiology of nephroblastoma, providing novel insights into the development of this disease. Moreover, these results offer new perspectives on the potential therapeutic targeting of AQP1 as a treatment strategy for nephroblastoma.

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Urinary KIM-1 and AQP-1 in patients with clear renal cell carcinoma: Potential noninvasive biomarkers

Abstract: uKIM-1 was found to be a reliable diagnostic marker of cRCC, based on its significantly increased values before and decreased values after the nephrectomy.

Cited by 5 publications

References 25 publications

Early detection of kidney cancer using urinary proteins: a truly non‐invasive strategy

Early detection of kidney cancer using urinary proteins: a truly non‐invasive strategy

KIM-1 (kidney injury molecule 1) in the urine of renal cell carcinoma patients

Overexpression of aquaporin-1 plays a vital role in proliferation, apoptosis, and pyroptosis of Wilms’ tumor cells

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