Page 32 - Read Online

Briggs et al. J Cancer Metastasis Treat 2021;7:46 Journal of Cancer
DOI: 10.20517/2394-4722.2021.84
Metastasis and Treatment

Review Open Access

Prognostic and predictive biomarkers for metastatic
renal cell carcinoma

1,3
1,2
1
Logan G. Briggs , Eugene B. Cone , Richard J. Lee , Michael L. Blute 1,2
1
Harvard Medical School, Boston, MA 02114, USA.
2
Department of Urology, Massachusetts General Hospital, Boston, MA 02114, USA.
3
Department of Medicine, Division of Hematology/Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
Correspondence to: Prof. Michael L. Blute, Urology Associates, Massachusetts General Hospital, 165 Cambridge Street, CPZ-7,
Boston, MA 02114, USA. E-mail: MBLUTE@mgh.harvard.edu
How to cite this article: Briggs LG, Cone EB, Lee RJ, Blute ML. Prognostic and predictive biomarkers for metastatic renal cell
carcinoma. J Cancer Metastasis Treat 2021;7:46. https://dx.doi.org/10.20517/2394-4722.2021.84

Received: 31 Mar 2021 First Decision: 9 Jun 2021 Revised: 15 Jun 2021 Accepted: 25 Jun 2021 First online: 2 Jul 2021
Academic Editors: Lucio Miele, Hendrik Van Poppel Copy Editor: Xi-Jun Chen Production Editor: Xi-Jun Chen

Abstract
Several prognostic models incorporating serum biomarkers to estimate patient survival have been established for
metastatic renal cell carcinoma. Interim advancements in biomarker research have highlighted much additional
serum, gene mutation, genetic expression signatures, and histologic biomarkers that predict clinical outcomes and
response to treatments. We, therefore, reviewed biomarkers associated with overall, cancer-specific, progression-
free, and disease-free survival, overall response, and time to treatment failure rate in adult populations with
metastatic renal cell carcinoma. We reviewed human studies reporting associations between biomarkers and
clinical outcomes. Data were abstracted via standardized form, then reported with hazard ratios and confidence
intervals where appropriate, subdivided by biomarker type (serum, gene mutation, genetic expression, and
histologic). We identified a range of newer biomarkers that have clinical associations with prognostic and
predictive outcomes. Beyond biomarkers used in modern risk models, those consistently associated with prognosis
included serum levels of CAIX, COP-NLR, CRP, s-TATI, and VEGF, gene mutations in BAP1, CDKN2A, CIMP/FH, and
TERT, gene expression of ERV and NQO1, and histologic macrophage infiltration and expression of CAIX and PDL1.
Biomarkers consistently associated with the response to targeted antiangiogenic therapy included serum CRP,
mutations in MET, PBRM-1, BAP1, and the mTOR pathway, TERT promoter mutations, and expression of PTEN and
angiogenic gene signatures. Gene expression of hERV, T-effector, and immunogenic signatures have been
associated with improved response to immune checkpoint inhibition. Future models should incorporate well-
studied biomarkers to help clinicians predict outcomes and treatment responses for patients with metastatic renal
cell carcinoma.

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

www.jcmtjournal.com