Serum and Urine Biomarkers for Human Renal Cell Carcinoma

Pastore, Antonio Luigi; Palleschi, Giovanni; Silvestri, Luigi; Moschese, Davide; Ricci, Serena; Petrozza, Vincenzo; Carbone, Antonio; Carlo, Angelina Di

doi:10.1155/2015/251403

Cited by 60 publications

(44 citation statements)

References 87 publications

(90 reference statements)

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“…Recent studies suggested that several prognostic models that were developed based on the TNM system may not effectively predict the postoperative prognosis of distinct RCC types, and the development of improved models with increased accuracy for recurrence patterns is sorely needed [10,11,12]. Additionally, diagnostic and prognostic molecular markers for RCC have not yet been fully incorporated into clinical practice [13,14]. …”

Section: Introductionmentioning

confidence: 99%

Mutations in the Mitochondrial ND1 Gene Are Associated with Postoperative Prognosis of Localized Renal Cell Carcinoma

Kim

Komiyama

Inomoto

et al. 2016

IJMS

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We analyzed mutations in the mitochondrial ND1 gene to determine their association with clinicopathological parameters and postoperative recurrence of renal cell carcinoma (RCC) in Japanese patients. Among 62 RCC cases for which tumor pathology was confirmed by histopathology, ND1 sequencing revealed the presence of 30 mutation sites in 19 cases. Most mutations were heteroplasmic, with 16 of 19 cases harboring one or more heteroplasmic sites. Additionally, 12 sites had amino acid mutations, which were frequent in 10 of the cases. The 5-year recurrence-free survival (RFS) rate was significantly worse in patients with tumors >40 mm in diameter (p = 0.0091), pathological T (pT) stage ≥3 (p = 0.0122), Fuhrman nuclear atypia grade ≥III (p = 0.0070), and ND1 mutations (p = 0.0006). Multivariate analysis using these factors revealed that mutations in ND1 were significantly associated with the 5-year RFS rate (p = 0.0044). These results suggest a strong correlation between the presence of ND1 mutations in cancer tissue and postoperative recurrence of localized RCC in Japanese patients.

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Section: Introductionmentioning

confidence: 99%

Mutations in the Mitochondrial ND1 Gene Are Associated with Postoperative Prognosis of Localized Renal Cell Carcinoma

Kim

Komiyama

Inomoto

et al. 2016

IJMS

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“…Obviously, biomarkers presented in blood are preferable than markers obtained from other tissues. For this purpose, many attempts have been performed aimed at recognizing novel informative RCC biomarkers applicable for early detection of the disease and a number of serological markers including VEGF, TATI have been reported to have diagnostic potential for early RCC [8,9]. However, their efficiency remains quite different and insufficient in sensitivity and/or specificity have limited their clinical feasibility.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the findings of routine diagnostic blood tests might be altered by RCC, but no change is pathognomonic. In addition, although several serum proteins have been ported to be able to detect the presence of advanced or recurrent RCC, unfortunately, none are used in the routine practice because they do not improve the diagnostic or prognostic accuracy [8,9]. Thus, there is an urgent need for the development new serum biomarkers and further introduction into clinical practice for RCC detection and monitoring, and in particular, accurate early diagnostic tools for RCC to obtain better treatment results.…”

Section: Introductionmentioning

confidence: 99%

Circulating miR-200a is a novel molecular biomarker for early-stage renal cell carcinoma

Wang

Ding

Zhu

et al. 2019

ExRNA

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Background: Circulating microRNAs (miRNAs) have been recognized as novel molecular markers for renal cell carcinoma (RCC) diagnosis. However, the clinical impact of circulating miRNA has rarely been evaluated for the early detection of RCC. Moreover, miRNAs also play important roles in regulating RCC tumorigenesis. The aim of this study is to assess the serum signatures of the epithelial-mesenchymal transition (EMT)-related miRNA-200 family in RCC patients and evaluate their diagnostic usefulness for early-stage RCC, and further explore the functions of specifically altered miRNAs that regulate pathological genes during the RCC tumorigenesis. Methods: The serum levels of three miR-200 miRNAs (miR-200a, miR-200b and miR-200c) were firstly measured in 26 RCC patients and 26 noncancer controls of the training phase using quantitative real-time polymerase chain reaction (RT-qPCR). Markedly dysregulated miRNAs in RCC patients were subsequently verified by RT-qPCR in an independent validation phase that consist of 73 patients and 73 controls. Differentially expressed miRNAs were further examined in RCC urine samples and corresponding controls. Additionally, the mechanisms underlying the altered miRNAs involved in RCC tumorigenesis were also elucidated. Results: Of the three examined miRNAs, only miR-200a showed consistently decreased levels in serum of the RCC patients, especially in those with stage I disease, as compared with controls (P < 0.001). MiR-200a is also frequently downregulated in RCC urine samples. Mechanistic investigations revealed that E2F3, an oncogene with strong proliferative and cell cycle regulation potential, is a direct target gene of miR-200a in RCC. E2F3 protein levels in RCC tissues and cell lines were increased and inversely associated with miR-200a levels. Upregulation of miR-200a decreased the expression of E2F3, with consequent repressed RCC cell proliferation and induced cell cycle arrest at G0/G1 phase in vitro. In contrast, inhibition of miR-200a in RCC cells resulted in increased expression of E2F3 and enhanced cell proliferation, and promoted G1/S transition. Conclusions: Serum miR-200a has the potential to be served as a novel noninvasive auxiliary diagnostic biomarker for the early detection of RCC, and the identified novel molecular interaction between miR-200a and E2F3 may provide insights into novel therapies for RCC.

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“…The identification of molecular markers in body fluids (e.g., sera and urine), which can be used as noninvasive diagnostic, prognostic and surveillance markers in ccRCC management, is one of the most ambitious challenges in oncologic research [20]. Of note, also miRNAs are acquiring a great potential as novel cancer biomarkers in urological carcinomas [16,[21][22][23][24][25].…”

Section: Discussionmentioning

confidence: 99%

Secreted miR-210-3p as non-invasive biomarker in clear cell renal cell carcinoma

Pastore¹,

Salhi²,

Fuschi³

et al. 2018

European Urology Supplements

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The most common subtype of renal cell carcinoma (RCC) is clear cell RCC (ccRCC). It accounts for 70-80% of all renal malignancies representing the third most common urological cancer after prostate and bladder cancer. The identification of non-invasive biomarkers for the diagnosis and responsiveness to therapy of ccRCC may represent a relevant step-forward in ccRCC management. The aim of this study is to evaluate whether specific miRNAs deregulated in ccRCC tissues present altered levels also in urine specimens. To this end we first assessed that miR-21-5p, miR-210-3p and miR-221-3p resulted upregulated in ccRCC fresh frozen tissues compared to matched normal counterparts. Next, we evidenced that miR-210-3p resulted significantly upregulated in 38 urine specimens collected from two independent cohorts of ccRCC patients at the time of surgery compared to healthy donors samples. Of note, miR-210-3p levels resulted significantly reduced in follow-up samples. These results point to miR-210-3p as a potential non-invasive biomarker useful not only for diagnosis but also for the assessment of complete resection or response to treatment in ccRCC management.

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Serum and Urine Biomarkers for Human Renal Cell Carcinoma

Cited by 60 publications

References 87 publications

Mutations in the Mitochondrial ND1 Gene Are Associated with Postoperative Prognosis of Localized Renal Cell Carcinoma

Mutations in the Mitochondrial ND1 Gene Are Associated with Postoperative Prognosis of Localized Renal Cell Carcinoma

Circulating miR-200a is a novel molecular biomarker for early-stage renal cell carcinoma

Secreted miR-210-3p as non-invasive biomarker in clear cell renal cell carcinoma

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