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Cell cycle progression score predicts metastatic progression of clear cell renal cell carcinoma after resection

Article type: Research Article

Authors: Askeland, Eric J.a | Chehval, Vincent A.a | Askeland, Ryan W.b | Fosso, Placede G.c | Sangale, Zainac | Xu, Nafeic | Rajamani, Saradhac | Stone, Stevenc | Brown, James A.a; *

Affiliations: [a] Department of Urology, University of Iowa, IA, USA | [b] Department of Pathology, University of Iowa, IA, USA | [c] Myriad Genetics, University of Iowa, IA, USA

Correspondence: [*] Corresponding author: James A. Brown, Department of Urology, University of Iowa, 200 Hawkins Dr., 3 RCP, Iowa City, IA 52242-1089, USA. Tel.: +1 319 384 7295; Fax: +1 319 356 3900; E-mail:james-brown-2@uiowa.edu

Keywords: Clear cell renal cell carcinoma, kidney cancer, metastasis, biological markers

DOI: 10.3233/CBM-150530

Journal: Cancer Biomarkers, vol. 15, no. 6, pp. 861-867, 2015

Published: 2015
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Abstract

BACKGROUND: The outcome of surgically resected, apparently localized, clear cell renal carcinoma (ccRCC) is uncertain.

OBJECTIVE: To evaluate if cell cycle progression (CCP) gene expression can predict future metastasis.

METHODS: Pathologic T2a-T3b tumors at University of Iowa were reviewed. Patients with known or suspected metastasis, lymph node involvement or who received neoadjuvant or adjuvant radiation, chemotherapy or immunotherapy were excluded. Case and control cohorts were defined as those who did or did not develop metastatic disease within 5 years. Measured levels of 31 cell cycle genes and 15 control genes from the tumor were calculated as a CCP score. Additionally, gene expression data for a separate ccRCC cohort was downloaded from The Cancer Genome Atlas (TCGA).

RESULTS: Univariate analysis of 26 cases and 38 controls revealed that the CCP score predicted progression to metastasis (OR 2.65, p = 0.0091). In multivariate logistic regression modeling, CCP expression remained a significant independent predictor for progression (p = 0.026). The CCP score was also significantly associated with distant metastasis in the TCGA renal cancer cohort in both univariate (p = 1.0 × 10-9) and multivariate (p = 5.6 × 10-3) analysis.

CONCLUSION: The CCP score has prognostic value in predicting metastatic progression after resection of organ-confined ccRCC.

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