TY - JOUR
T1 - MicroRNA profile in stage I clear cell renal cell carcinoma predicts progression to metastatic disease
AU - Moynihan, Matthew J.
AU - Sullivan, Travis B.
AU - Burks, Eric
AU - Schober, Jared
AU - Calabrese, Marc
AU - Fredrick, Ariel
AU - Kalantzakos, Thomas
AU - Warrick, Joshua
AU - Canes, David
AU - Raman, Jay D.
AU - Rieger-Christ, Kimberly
N1 - Funding Information:
This work was supported in part by funding from the R.K. Mellon Family Foundation , the Thea Post Foundation , a grant from the Morton E. Goulder Research Endowment Fund , as well as the Keith and Lynda Haring Fund for Kidney Cancer Research .
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/10
Y1 - 2020/10
N2 - Objective: This study sought to identify microRNA (miRNA) profiles of small, pathologically confirmed stage 1 clear cell renal cell carcinoma (ccRCC) tumors that are associated with progression to metachronous metastatic disease. Materials and methods: Fifty-five pathologic stage 1 ccRCC tumors ≤5cm, from 2 institutions, were examined in a miRNA screening, followed by a validation study. For the screening phase 752 miRNA were evaluated on each sample to identify those with differential expression between tumors that subsequently did (n = 10) or did not (n = 10) progress to metastatic disease. For the validation, 35 additional samples (20 nonprogressors and 15 with distant progression) were utilized to investigate 20 miRNA to determine if a miRNA panel could differentiate aggressive tumors: associations of miRNA expression with cancer specific survival was also investigated. Results: In the screening analysis, 35 miRNA were differentially expressed (P < 0.05, FDR < 0.1) between the groups. In the validation, 11 miRNA were confirmed to have differential expression. The miRNA -10a-5p, -23b-3p, and -26a-5p differentiated nonprogressive and distant progressive disease with a sensitivity of 73.3% and a specificity of 85% (AUC=0.893). In addition, levels of miR-30a-3p and -145-5p were identified as independent prognostic factors of cancer specific survival. Conclusions: This investigation identified miRNA biomarkers that may differentiate between non-progressive ccRCC tumors and those that progress to metastatic disease in this group of stage I tumors. The miRNA profiles determined in this study have the potential to identify patients with small renal masses who are likely to have progressive ccRCC. Such information may be valuable to incorporate into predictive models.
AB - Objective: This study sought to identify microRNA (miRNA) profiles of small, pathologically confirmed stage 1 clear cell renal cell carcinoma (ccRCC) tumors that are associated with progression to metachronous metastatic disease. Materials and methods: Fifty-five pathologic stage 1 ccRCC tumors ≤5cm, from 2 institutions, were examined in a miRNA screening, followed by a validation study. For the screening phase 752 miRNA were evaluated on each sample to identify those with differential expression between tumors that subsequently did (n = 10) or did not (n = 10) progress to metastatic disease. For the validation, 35 additional samples (20 nonprogressors and 15 with distant progression) were utilized to investigate 20 miRNA to determine if a miRNA panel could differentiate aggressive tumors: associations of miRNA expression with cancer specific survival was also investigated. Results: In the screening analysis, 35 miRNA were differentially expressed (P < 0.05, FDR < 0.1) between the groups. In the validation, 11 miRNA were confirmed to have differential expression. The miRNA -10a-5p, -23b-3p, and -26a-5p differentiated nonprogressive and distant progressive disease with a sensitivity of 73.3% and a specificity of 85% (AUC=0.893). In addition, levels of miR-30a-3p and -145-5p were identified as independent prognostic factors of cancer specific survival. Conclusions: This investigation identified miRNA biomarkers that may differentiate between non-progressive ccRCC tumors and those that progress to metastatic disease in this group of stage I tumors. The miRNA profiles determined in this study have the potential to identify patients with small renal masses who are likely to have progressive ccRCC. Such information may be valuable to incorporate into predictive models.
KW - Biomarkers
KW - Clear cell renal cell cancer (ccRCC)
KW - Metastasis
KW - microRNA
KW - Progression
UR - http://www.scopus.com/inward/record.url?scp=85086150318&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086150318&partnerID=8YFLogxK
U2 - 10.1016/j.urolonc.2020.05.006
DO - 10.1016/j.urolonc.2020.05.006
M3 - Article
C2 - 32534961
AN - SCOPUS:85086150318
SN - 1078-1439
VL - 38
SP - 799.e11-799.e22
JO - Urologic Oncology: Seminars and Original Investigations
JF - Urologic Oncology: Seminars and Original Investigations
IS - 10
ER -