TY - JOUR
T1 - Cell-free plasma microRNAs that identify patients with glioblastoma
AU - Bustos, Matias A.
AU - Rahimzadeh, Negin
AU - Ryu, Suyeon
AU - Gross, Rebecca
AU - Tran, Linh T.
AU - Renteria-Lopez, Victor M.
AU - Ramos, Romela I.
AU - Eisenberg, Amy
AU - Hothi, Parvinder
AU - Kesari, Santosh
AU - Barkhoudarian, Garni
AU - Takasumi, Yuki
AU - Cobbs, Charles
AU - Kelly, Daniel F.
AU - Hoon, Dave S.B.
N1 - Funding Information:
The authors thank the Department of Translational Molecular Medicine staff at SJCI, the Cancer Clinic, the Department of Pathology, PNI staff at SJHC, and Ivy Center research staff at Swedish Medical Center for their kind advisory and technical assistance.
Funding Information:
This research was funded by the Gonda Foundation to D.S.B.H. The work performed at Swedish Medical Center was supported by the Ivy Center’s Philanthropic Research Fund.
Publisher Copyright:
© 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
PY - 2022/7
Y1 - 2022/7
N2 - Glioblastoma (GBM) is still one of the most commonly diagnosed advanced stage primary brain tumors. Current treatments for patients with primary GBM (pGBM) are often not effective and a significant proportion of the patients with pGBM recur. The effective treatment options for recurrent GBM (rGBM) are limited and survival outcomes are poor. This retrospective multicenter pilot study aims to determine potential cell-free microRNAs (cfmiRs) that identify patients with pGBM and rGBM tumors. 2,083 miRs were assessed using the HTG miRNA whole transcriptome assay (WTA). CfmiRs detection was compared in pre-operative plasma samples from patients with pGBM (n = 32) and rGBM (n = 13) to control plasma samples from normal healthy donors (n = 73). 265 cfmiRs were found differentially expressed in plasma samples from pGBM patients compared to normal healthy donors (FDR < 0.05). Of those 193 miRs were also detected in pGBM tumor tissues (n = 15). Additionally, we found 179 cfmiRs differentially expressed in rGBM, of which 68 cfmiRs were commonly differentially expressed in pGBM. Using Random Forest algorithm, specific cfmiR classifiers were found in the plasma of pGBM, rGBM, and both pGBM and rGBM combined. Two common cfmiR classifiers, miR-3180-3p and miR-5739, were found in all the comparisons. In receiving operating characteristic (ROC) curves analysis for rGBM miR-3180-3p showed a specificity of 87.7% and a sensitivity of 100% (AUC = 98.5%); while miR-5739 had a specificity of 79.5% and sensitivity of 92.3% (AUC = 90.2%). This study demonstrated that plasma samples from pGBM and rGBM patients have specific miR signatures. CfmiR-3180-3p and cfmiR-5739 have potential utility in diagnosing patients with pGBM and rGBM tumors using a minimally invasive blood assay.
AB - Glioblastoma (GBM) is still one of the most commonly diagnosed advanced stage primary brain tumors. Current treatments for patients with primary GBM (pGBM) are often not effective and a significant proportion of the patients with pGBM recur. The effective treatment options for recurrent GBM (rGBM) are limited and survival outcomes are poor. This retrospective multicenter pilot study aims to determine potential cell-free microRNAs (cfmiRs) that identify patients with pGBM and rGBM tumors. 2,083 miRs were assessed using the HTG miRNA whole transcriptome assay (WTA). CfmiRs detection was compared in pre-operative plasma samples from patients with pGBM (n = 32) and rGBM (n = 13) to control plasma samples from normal healthy donors (n = 73). 265 cfmiRs were found differentially expressed in plasma samples from pGBM patients compared to normal healthy donors (FDR < 0.05). Of those 193 miRs were also detected in pGBM tumor tissues (n = 15). Additionally, we found 179 cfmiRs differentially expressed in rGBM, of which 68 cfmiRs were commonly differentially expressed in pGBM. Using Random Forest algorithm, specific cfmiR classifiers were found in the plasma of pGBM, rGBM, and both pGBM and rGBM combined. Two common cfmiR classifiers, miR-3180-3p and miR-5739, were found in all the comparisons. In receiving operating characteristic (ROC) curves analysis for rGBM miR-3180-3p showed a specificity of 87.7% and a sensitivity of 100% (AUC = 98.5%); while miR-5739 had a specificity of 79.5% and sensitivity of 92.3% (AUC = 90.2%). This study demonstrated that plasma samples from pGBM and rGBM patients have specific miR signatures. CfmiR-3180-3p and cfmiR-5739 have potential utility in diagnosing patients with pGBM and rGBM tumors using a minimally invasive blood assay.
UR - http://www.scopus.com/inward/record.url?scp=85122666165&partnerID=8YFLogxK
U2 - 10.1038/s41374-021-00720-4
DO - 10.1038/s41374-021-00720-4
M3 - Article
C2 - 35013528
AN - SCOPUS:85122666165
SN - 0023-6837
VL - 102
SP - 711
EP - 721
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 7
ER -