Advancements in the identification of EV derived mRNA biomarkers for liquid biopsy of clear cell renal cell carcinomas - 22/02/22

Doi : 10.1016/j.urology.2021.11.002

Morgan D. Kuczler ^a,^{^{#
authors contributed equally to this work},}^⁎ , Richard C. Zieren ^a,^b,^{^{#
authors contributed equally to this work}}, Liang Dong ^a,^c, Theo M. de Reijke ^b, Kenneth J. Pienta ^a, Sarah R. Amend ^a
^a The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland
^b Department of Urology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
^c Department of Urology, Renji Hospital, Shanghai Jiao Tong University of Medicine, Shanghai, China

^⁎Address correspondence to: Morgan D. Kuczler, BA, The James Buchanan Brady Urological Institute at the Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287.The James Buchanan Brady Urological Institute at the Johns Hopkins University School of Medicine600 North Wolfe StreetBaltimoreMD21287

Abstract

Objective

To propose EV-derived mRNA as a potential diagnostic biomarker detecting the presence of clear cell renal cell carcinoma (ccRCC). There is currently no kidney cancer specific screening or diagnostic technology. Therefore, one-third of kidney cancer diagnoses occur after the cancer has metastasized and is past curative measures

Materials and Methods

Urine, plasma, normal tumor adjacent tissue, and tumor tissue was collected from a limited population of ccRCC patients. Extracellular vesicle (EV) isolation was performed on each sample, followed by mRNA extraction from isolated EVs. NanoString nCounter technology was utilized to count the mRNA transcripts present in matched plasma, urine, tumor tissue, and normal tumor adjacent tissue samples.

Results

770 mRNA transcripts related to gene's affecting cancer's progression and metastasis processes were evaluated. Four EV derived mRNA transcripts (ALOX5, RBL2, VEGFA, TLK2) were found specific to urine and tumor tissue samples.

Conclusion

Four candidate RCC-specific urine EV biomarkers were identified. However, due to the lack of a true negative control and urine collection techniques, further re-examination is necessary for validation. This study demonstrates the promise of defining disease-specific EV biomarkers in liquid biopsy patient samples.

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Abbreviations : ccRCC, EV, RT, TCM, SEC, ALOX5, RBL2, VEGFA, TLK2

Plan

METHODS AND MATERIALS

Sample Collection

Tissue-Conditioned Media for EV Isolation

EV Isolation from Patient Samples

mRNA Isolation from Sample Derived EVs

mRNA Expression Profiling Using Nanostring

Analysis of EV Derived mRNA Transcript Counts

RESULTS

mRNA EV Cargo from ccRCC Patient Tumor, Tumor Adjacent Tissue, Plasma, and Urine

Defining an RCC-Specific EV mRNA Signature

EV Derived mRNA Transcripts in Patients Receiving Immunotherapy Prior to Collection

DISCUSSION

CONCLUSION

	Financial Disclosure: KJ Pienta is a consultant for CUE Biopharma, Inc., is a founder and holds equity interest in Keystone Biopharma, Inc., and receives research support from Progenics, Inc. SR Amend also holds equity interest in Keystone Biopharma, Inc. The other authors declare no conflicts of interest.
	Funding Support: This work was funded by US Department of Defense CDMRP/PCRP (W81XWH-20-10353), the Patrick C. Walsh Prostate Cancer Research Fund and the Prostate Cancer Foundation to SR Amend; and NCI grants U54CA143803, CA163124, CA093900, and CA143055, and the Prostate Cancer Foundation to KJ Pienta.

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Vol 160

P. 87-93 - février 2022 Retour au numéro

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Advancements in the identification of EV derived mRNA biomarkers for liquid biopsy of clear cell renal cell carcinomas - 22/02/22

Abstract

Objective

Materials and Methods

Results

Conclusion

Plan

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