Urine Molecular Biomarkers for Detection and Follow-Up of Small Renal Masses

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Dec 23

PMID 36555747

Authors

Algirdas Zalimas

Raimonda Kubiliute

Kristina Zukauskaite

Rasa Sabaliauskaite

Mantas Trakymas

Simona Letautiene

Edita Miseikyte Kaubriene

Jurgita Usinskiene

Albertas Ulys

Sonata Jarmalaite

Affiliations

Soon will be listed here.

Abstract

Active surveillance (AS) is the best strategy for small renal masses (SRMs) management; however, reliable methods for early detection and disease aggressiveness prediction are urgently needed. The aim of the present study was to validate DNA methylation biomarkers for non-invasive SRM detection and prognosis. The levels of methylated genes , , , , and were evaluated in 165 serial urine samples prospectively collected from 39 patients diagnosed with SRM, specifically renal cell carcinoma (RCC), before and during the AS via quantitative methylation-specific polymerase chain reaction. Voided urine samples from 92 asymptomatic volunteers were used as the control. Significantly higher methylated , , , and levels and/or frequencies were detected in SRM patients' urine samples as compared to the control. The highest diagnostic power (AUC = 0.74) was observed for the four biomarkers panel with 92% sensitivity and 52% specificity. Methylated level positively correlated with SRM size at diagnosis, while had the opposite effect and was related to SRM progression. To sum up, SRMs contribute significantly to the amount of methylated DNA detectable in urine, which might be used for very early RCC detection. Moreover, and methylation have the potential to be prognostic biomarkers for SRMs.

Citing Articles

Detection and Validation of Organic Metabolites in Urine for Clear Cell Renal Cell Carcinoma Diagnosis.

Holbrook K, Quaye G, Noriega Landa E, Su X, Gao Q, Williams H Metabolites. 2024; 14(10).

PMID: 39452927 PMC: 11509871. DOI: 10.3390/metabo14100546.

References

Grant O, Wang Y, Kumari M, Zabet N, Schalkwyk L . Characterising sex differences of autosomal DNA methylation in whole blood using the Illumina EPIC array. Clin Epigenetics. 2022; 14(1):62. PMC: 9107695. DOI: 10.1186/s13148-022-01279-7. View

Park S, Park B, Kim C, Kwon G . Ultrasound-guided core biopsy of small renal masses: diagnostic rate and limitations. J Vasc Interv Radiol. 2012; 24(1):90-6. DOI: 10.1016/j.jvir.2012.09.007. View

Di Meo A, Batruch I, Brown M, Yang C, Finelli A, Jewett M . Searching for prognostic biomarkers for small renal masses in the urinary proteome. Int J Cancer. 2019; 146(8):2315-2325. DOI: 10.1002/ijc.32650. View

Sohlberg E, Metzner T, Leppert J . The Harms of Overdiagnosis and Overtreatment in Patients with Small Renal Masses: A Mini-review. Eur Urol Focus. 2019; 5(6):943-945. DOI: 10.1016/j.euf.2019.03.006. View

Turajlic S, Xu H, Litchfield K, Rowan A, Horswell S, Chambers T . Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal. Cell. 2018; 173(3):595-610.e11. PMC: 5938372. DOI: 10.1016/j.cell.2018.03.043. View

Daniunaite K, Jarmalaite S, Kalinauskaite N, Petroska D, Laurinavicius A, Lazutka J . Prognostic value of RASSF1 promoter methylation in prostate cancer. J Urol. 2014; 192(6):1849-55. DOI: 10.1016/j.juro.2014.06.075. View

Gill I, Aron M, Gervais D, Jewett M . Clinical practice. Small renal mass. N Engl J Med. 2010; 362(7):624-34. DOI: 10.1056/NEJMcp0910041. View

McIntosh A, Ristau B, Ruth K, Jennings R, Ross E, Smaldone M . Active Surveillance for Localized Renal Masses: Tumor Growth, Delayed Intervention Rates, and >5-yr Clinical Outcomes. Eur Urol. 2018; 74(2):157-164. DOI: 10.1016/j.eururo.2018.03.011. View

Volpe A, Panzarella T, Rendon R, Haider M, Kondylis F, Jewett M . The natural history of incidentally detected small renal masses. Cancer. 2004; 100(4):738-45. DOI: 10.1002/cncr.20025. View

10.

Menon A, Hussein A, Attwood K, White T, James G, Xu B . Active Surveillance for Risk Stratification of All Small Renal Masses Lacking Predefined Clinical Criteria for Intervention. J Urol. 2021; 206(2):229-239. PMC: 9036570. DOI: 10.1097/JU.0000000000001714. View

11.

Kubiliute R, Zukauskaite K, Zalimas A, Ulys A, Sabaliauskaite R, Bakavicius A . Clinical significance of novel DNA methylation biomarkers for renal clear cell carcinoma. J Cancer Res Clin Oncol. 2021; 148(2):361-375. DOI: 10.1007/s00432-021-03837-7. View

12.

Kubiliute R, Jarmalaite S . Epigenetic Biomarkers of Renal Cell Carcinoma for Liquid Biopsy Tests. Int J Mol Sci. 2021; 22(16). PMC: 8396354. DOI: 10.3390/ijms22168846. View

13.

Ibragimova I, Slifker M, Maradeo M, Banumathy G, Dulaimi E, Uzzo R . Genome-wide promoter methylome of small renal masses. PLoS One. 2013; 8(10):e77309. PMC: 3811999. DOI: 10.1371/journal.pone.0077309. View

14.

Whelan E, Mason R, Himmelman J, Matheson K, Rendon R . Extended Duration of Active Surveillance of Small Renal Masses: A Prospective Cohort Study. J Urol. 2019; 202(1):57-61. DOI: 10.1097/JU.0000000000000075. View

15.

Chopra S, Liu J, Alemozaffar M, Nichols P, Aron M, Weisenberger D . Improving needle biopsy accuracy in small renal mass using tumor-specific DNA methylation markers. Oncotarget. 2016; 8(3):5439-5448. PMC: 5354921. DOI: 10.18632/oncotarget.12276. View

16.

Wang L, Wang C, Wu T, Sun F . Long non-coding RNA TP73-AS1 promotes TFAP2B-mediated proliferation, metastasis and invasion in retinoblastoma via decoying of miRNA-874-3p. J Cell Commun Signal. 2020; 14(2):193-205. PMC: 7272539. DOI: 10.1007/s12079-020-00550-x. View

17.

Yu J, Koujak S, Nagase S, Li C, Su T, Wang X . PCDH8, the human homolog of PAPC, is a candidate tumor suppressor of breast cancer. Oncogene. 2008; 27(34):4657-65. PMC: 3013056. DOI: 10.1038/onc.2008.101. View

18.

Marchioni M, Martel T, Bandini M, Pompe R, Tian Z, Kapoor A . Marital status and gender affect stage, tumor grade, treatment type and cancer specific mortality in T N M renal cell carcinoma. World J Urol. 2017; 35(12):1899-1905. DOI: 10.1007/s00345-017-2082-9. View

19.

Arai E, Kanai Y . Genetic and epigenetic alterations during renal carcinogenesis. Int J Clin Exp Pathol. 2011; 4(1):58-73. PMC: 3016104. View

20.

Chen W, Zhuang J, Wang P, Jiang J, Lin C, Zeng P . DNA methylation-based classification and identification of renal cell carcinoma prognosis-subgroups. Cancer Cell Int. 2019; 19:185. PMC: 6636124. DOI: 10.1186/s12935-019-0900-4. View