Small EVs-Associated DNA as Complementary Biomarker to Circulating Tumor DNA in Plasma of Metastatic Colorectal Cancer Patients

Pharmaceuticals

卷:14

Silvia Galbiati¹  Valentina Burgio²  Monica Ronzoni²  Marcella Chiari³  Dario Brambilla³  Lucia Ferraro³  AnnaM. Ferretti³  Laura Sola³  Francesco Damin³  Nadia Soriani⁴  Riccardo Vago⁵ 

[1] Complications of Diabetes Units, Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy;

[2] Dipartimento di Oncologia Medica, IRCCS Ospedale San Raffaele, 20132 Milan, Italy;

[3] Istituto di Scienze e Tecnologie Chimiche “Giulio Natta” SCITEC CNR, 20131 Milan, Italy;

[4] Unit of Genomic for the Diagnosis of Human Pathologies, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy;

[5] Urological Research Institute, Division of Experimental Oncology, IRCCS Ospedale San Raffaele, 20132 Milan, Italy;

关键词: exosomes;    extracellular vesicles;    liquid biopsy;    cancer biomarkers;    ddPCR;    microarray;   

DOI  :  10.3390/ph14020128

来源: DOAJ

【 摘 要 】

It is widely accepted that assessing circular tumor DNA (ctDNA) in the plasma of cancer patients is a promising practice to evaluate somatic mutations from solid tumors noninvasively. Recently, it was reported that isolation of extracellular vesicles improves the detection of mutant DNA from plasma in metastatic patients; however, no consensus on the presence of dsDNA in exosomes has been reached yet. We analyzed small extracellular vesicle (sEV)-associated DNA of eleven metastatic colorectal cancer (mCRC) patients and compared the results obtained by microarray and droplet digital PCR (ddPCR) to those reported on the ctDNA fraction. We detected the same mutations found in tissue biopsies and ctDNA in all samples but, unexpectedly, in one sample, we found a KRAS mutation that was not identified either in ctDNA or tissue biopsy. Furthermore, to assess the exact location of sEV-associated DNA (outside or inside the vesicle), we treated with DNase I sEVs isolated with three different methodologies. We found that the DNA inside the vesicles is only a small fraction of that surrounding the vesicles. Its amount seems to correlate with the total amount of circulating tumor DNA. The results obtained in our experimental setting suggest that integrating ctDNA and sEV-associated DNA in mCRC patient management could provide a complete real-time assessment of the cancer mutation status.

【 授权许可】

Unknown