Circulating exosomal mRNA signatures for the early diagnosis of clear cell renal cell carcinoma.
Clear cell renal cell carcinoma
Diagnosis
Exosome
Signature
mRNA
Journal
BMC medicine
ISSN: 1741-7015
Titre abrégé: BMC Med
Pays: England
ID NLM: 101190723
Informations de publication
Date de publication:
25 08 2022
25 08 2022
Historique:
received:
23
03
2022
accepted:
04
07
2022
entrez:
24
8
2022
pubmed:
25
8
2022
medline:
27
8
2022
Statut:
epublish
Résumé
There are no proven tumor biomarkers for the early diagnosis of clear cell renal cell carcinoma (ccRCC) thus far. This study aimed to identify novel biomarkers of ccRCC based on exosomal mRNA (emRNA) profiling and develop emRNA-based signatures for the early detection of ccRCC. Four hundred eighty-eight participants, including 226 localized ccRCCs, 73 patients with benign renal masses, and 189 healthy controls, were recruited. Circulating emRNA sequencing was performed in 12 ccRCCs and 22 healthy controls in the discovery phase. The candidate emRNAs were evaluated with 108 ccRCCs and 70 healthy controls in the test and training phases. The emRNA-based signatures were developed by logistic regression analysis and validated with additional cohorts of 106 ccRCCs, 97 healthy controls, and 73 benign individuals. Five emRNAs, CUL9, KMT2D, PBRM1, PREX2, and SETD2, were identified as novel potential biomarkers of ccRCC. We further developed an early diagnostic signature that comprised KMT2D and PREX2 and a differential diagnostic signature that comprised CUL9, KMT2D, and PREX2 for RCC detection. The early diagnostic signature displayed high accuracy in distinguishing ccRCCs from healthy controls, with areas under the receiver operating characteristic curve (AUCs) of 0.836 and 0.830 in the training and validation cohorts, respectively. The differential diagnostic signature also showed great performance in distinguishing ccRCCs from benign renal masses (AUC = 0.816), including solid masses (AUC = 0.810) and cystic masses (AUC = 0.832). We established and validated novel emRNA-based signatures for the early detection of ccRCC and differential diagnosis of uncertain renal masses. These signatures could be promising and noninvasive biomarkers for ccRCC detection and thus improve the prognosis of ccRCC patients.
Sections du résumé
BACKGROUND
There are no proven tumor biomarkers for the early diagnosis of clear cell renal cell carcinoma (ccRCC) thus far. This study aimed to identify novel biomarkers of ccRCC based on exosomal mRNA (emRNA) profiling and develop emRNA-based signatures for the early detection of ccRCC.
METHODS
Four hundred eighty-eight participants, including 226 localized ccRCCs, 73 patients with benign renal masses, and 189 healthy controls, were recruited. Circulating emRNA sequencing was performed in 12 ccRCCs and 22 healthy controls in the discovery phase. The candidate emRNAs were evaluated with 108 ccRCCs and 70 healthy controls in the test and training phases. The emRNA-based signatures were developed by logistic regression analysis and validated with additional cohorts of 106 ccRCCs, 97 healthy controls, and 73 benign individuals.
RESULTS
Five emRNAs, CUL9, KMT2D, PBRM1, PREX2, and SETD2, were identified as novel potential biomarkers of ccRCC. We further developed an early diagnostic signature that comprised KMT2D and PREX2 and a differential diagnostic signature that comprised CUL9, KMT2D, and PREX2 for RCC detection. The early diagnostic signature displayed high accuracy in distinguishing ccRCCs from healthy controls, with areas under the receiver operating characteristic curve (AUCs) of 0.836 and 0.830 in the training and validation cohorts, respectively. The differential diagnostic signature also showed great performance in distinguishing ccRCCs from benign renal masses (AUC = 0.816), including solid masses (AUC = 0.810) and cystic masses (AUC = 0.832).
CONCLUSIONS
We established and validated novel emRNA-based signatures for the early detection of ccRCC and differential diagnosis of uncertain renal masses. These signatures could be promising and noninvasive biomarkers for ccRCC detection and thus improve the prognosis of ccRCC patients.
Identifiants
pubmed: 36002886
doi: 10.1186/s12916-022-02467-1
pii: 10.1186/s12916-022-02467-1
pmc: PMC9404613
doi:
Substances chimiques
Biomarkers, Tumor
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
270Informations de copyright
© 2022. The Author(s).
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