A serum three-microRNA panel: promising biomarkers for renal cell carcinoma screening

Abstract

Aim: Renal cell carcinoma (RCC) screening is helpful to improve the prognosis of patients. However, the existing RCC detection methods are not suitable for large-scale screening. Serum microRNAs (miRNAs) is expected to be a convenient, economical, and non-invasive screening tool for RCC. This study aimed to identify relevant serum miRNAs as diagnostic markers for RCC.

Methods: This research included 112 patients with RCC and 112 healthy control individuals, carried out in three distinct phases. The objective was to identify serum miRNAs suitable for RCC diagnosis using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Additionally, bioinformatics analyses were performed to predict target genes and provide functional annotations.

Results: Compared with healthy controls, patients with RCC highly expressed miR-221-3p and lowly expressed miR-124-3p, let-7b-5p, miR-30a-5p, and miR-302d-3p. After multiple rounds of combination screening, the combination of miR-124-3p, miR-221-3p, and let-7b-5p showed good diagnostic predictability. The diagnostic panel exhibited a 0.838 area under curve (AUC), achieving 75.00% sensitivity and 77.68% specificity.

Conclusion: Our analysis demonstrates that combining miR-124-3p, let-7b-5p, and miR-221-3p forms a non-invasive, economical, and remarkably effective diagnostic indicator for patients with renal cell carcinoma.

Keywords

microRNA / miR-221-3p / let-7b-5p / renal cell carcinoma / miR-124-3p / biomarker

References

[1] Miller KD,Ortiz AP.Cancer statistics for hispanics/latinos, 2018.CA Cancer J Clin2018;68:425-45

[2] Sung H,Siegel RL.Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J Clin2021;71:209-49

[3] Hsieh JJ,Signoretti S.Renal cell carcinoma.Nat Rev Dis Primers2017;3:17009 PMCID:PMC5936048

[4] Warren AY.WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: standards and controversies.World J Urol2018;36:1913-26 PMCID:PMC6280811

[5] Pandolfo SD,Campi R.Outcomes and techniques of robotic-assisted partial nephrectomy (RAPN) for renal hilar masses: a comprehensive systematic review.Cancers2024;16:693 PMCID:PMC10886610

[6] Fiorentino V,Larocca LM,Martini M.First-line ICIs in renal cell carcinoma.Hum Vaccin Immunother2023;19:2225386 PMCID:PMC10332208

[7] Gill DM,Hale P.Overview of current and future first-line systemic therapy for metastatic clear cell renal cell carcinoma.Curr Treat Options Oncol2018;19:6

[8] Larroquette M,Domblides C.Adjuvant therapy in renal cell carcinoma: current knowledges and future perspectives.Cancer Treat Rev2021;97:102207

[9] Vasudev NS,Stewart GD.Challenges of early renal cancer detection: symptom patterns and incidental diagnosis rate in a multicentre prospective UK cohort of patients presenting with suspected renal cancer.BMJ Open2020;10:e035938 PMCID:PMC7223292

[10] Pavlakis GM,Anagnostopoulos GK.Intestinal metastases from renal cell carcinoma: a rare cause of intestinal obstruction and bleeding.Mt Sinai J Med2004;71:127-30

[11] Campbell S,Allaf ME.Renal mass and localized renal cancer: AUA guideline.J Urol2017;198:520-9

[12] Ruppert-Kohlmayr AJ,Meissnitzer T.Differentiation of renal clear cell carcinoma and renal papillary carcinoma using quantitative CT enhancement parameters.AJR Am J Roentgenol2004;183:1387-91

[13] Cimadamore A,Di Loreto C.Predictive and prognostic biomarkers in urological tumours.Pathology2024;56:228-38

[14] Kirschner MB,Edelman JJ.Haemolysis during sample preparation alters microRNA content of plasma.PLoS One2011;6:e24145 PMCID:PMC3164711

[15] Gopalan V,Lam AK.Downregulation of microRNA-498 in colorectal cancers and its cellular effects.Exp Cell Res2015;330:423-8

[16] Ghasemi E,Almasi-Hashiani A.The significance of miR-124 in the diagnosis and prognosis of glioma: a systematic review.PLoS One2024;19:e0312250 PMCID:PMC11530070

[17] Long C,Li J.The diagnostic accuracy of urine-derived exosomes for bladder cancer: a systematic review and meta-analysis.World J Surg Oncol2024;22:285 PMCID:PMC11520875

[18] Park JS,Hyun DH.Revisiting the diagnostic performance of exosomes: harnessing the feasibility of combinatorial exosomal miRNA profiles for colorectal cancer diagnosis.Discov Oncol2024;15:605 PMCID:PMC11525371

[19] Dweep H.miRWalk2.0: a comprehensive atlas of microRNA-target interactions.Nat Methods2015;12:697

[20] Livak KJ.Analysis of relative gene expression data using real-time quantitative PCR and the 2^-ΔΔCT method.Methods2001;25:402-8

[21] Piperigkou Z.Dynamic Interplay between miRNAs and the Extracellular Matrix Influences the Tumor Microenvironment.Trends Biochem Sci2019;44:1076-88

[22] Zhang C,Xu X.Cancer diagnosis with DNA molecular computation.Nat Nanotechnol2020;15:709-15

[23] Zhou X,Xu M.Comprehensive analysis of PTEN-related ceRNA network revealing the key pathways WDFY3-AS2 - miR-21-5p/miR-221-3p/miR-222-3p - TIMP3 as potential biomarker in tumorigenesis and prognosis of kidney renal clear cell carcinoma.Mol Carcinog2022;61:508-23

[24] Friedrich M,Stoehr C.CREB1 is affected by the microRNAs miR-22-3p, miR-26a-5p, miR-27a-3p, and miR-221-3p and correlates with adverse clinicopathological features in renal cell carcinoma.Sci Rep2020;10:6499 PMCID:PMC7162877

[25] Gao C,Chen H,Wang B.Long non-coding RNA nuclear paraspeckle assembly transcript 1 (NEAT1)relieves sepsis-induced kidney injury and lipopolysaccharide (LPS)-induced inflammation in HK-2 cells.Med Sci Monit2020;26:e921906 PMCID:PMC7414528

[26] Oghumu S,Nori U.Acute pyelonephritis in renal allografts-a new role for microRNAs?.Transplantation2014;97:559-68 PMCID:PMC4090250

[27] Wang SY,Hong Q,Cai GY.Mesenchymal stem cells ameliorate cisplatin-induced acute kidney injury via let-7b-5p.Cell Tissue Res2023;392:517-33

[28] Dai Y,Li X.Let-7b-5p inhibits colon cancer progression by prohibiting APC ubiquitination degradation and the Wnt pathway by targeting NKD1.Cancer Sci2023;114:1882-97 PMCID:PMC10154867

[29] Huang X,Liu Y.Silencing of let-7b-5p inhibits ovarian cancer cell proliferation and stemness characteristics by Asp-Glu-Ala-Asp-box helicase 19A.Bioengineered2021;12:7666-77 PMCID:PMC8806929

[30] Zhang X,Zeng Z.Bioinformatic analysis identifying FGF1 gene as a new prognostic indicator in clear cell renal cell carcinoma.Cancer Cell Int2021;21:222 PMCID:PMC8052755

[31] Jingushi K,Nakano K.Leukocyte-associated immunoglobulin-like receptor 1 promotes tumorigenesis in RCC.Oncol Rep2019;41:1293-303

[32] Gan J.PTPRO predicts patient prognosis and correlates with immune infiltrates in human clear cell renal cell carcinoma.Transl Cancer Res2020;9:4800-10 PMCID:PMC8798001

[33] Xu CL,Li D,Sha ML.Acyl-CoA thioesterase 8 and 11 as novel biomarkers for clear cell renal cell carcinoma.Front Genet2020;11:594969 PMCID:PMC7758486

[34] Zhong G,Luo Y.FECH expression correlates with the prognosis and tumor immune microenvironment in clear cell renal cell carcinoma.J Oncol2022;2022:8943643 PMCID:PMC9436586

[35] Weygant N,May R.DCLK1 is a broadly dysregulated target against epithelial-mesenchymal transition, focal adhesion, and stemness in clear cell renal carcinoma.Oncotarget2015;6:2193-205 PMCID:PMC4385845

[36] Zhao TL,Bao Y,Liu B.GRK5 promotes tumor progression in renal cell carcinoma.Neoplasma2019;66:261-70