Open Access Peer-reviewed Research Article

C-Reactive Protein in Solid Tumors: Clinically Meaningful Change

Main Article Content

Wael Lasheen corresponding author
Declan Walsh

Abstract

Background: C-Reactive Protein (CRP) is associated with cancer development, survival, and tumor recurrence. A barrier to its use is the inability to interpret changes in CRP levels.
Aims: The aim of this study was to determine when a change in CRP is clinically meaningful. Methods: This was a retrospective cohort study of consecutive cancer patients. Those with a solid tumor diagnosis and at least two consecutive CRP measurements postdiagnosis were included. Subjects were divided into Baseline High CRP (bHCRP; CRP ≥ 10 mg/L) and Baseline Normal CRP groups (bNCRP; CRP < 10 mg/L), We identified appropriate CRP cut-off points for CRP levels changes; compared bHCRP and bNCRP; constructed Kaplan- Meier survival plots and Cox Proportional Hazard Model to confirm cut-off points in each group.
Results: 1473 were eligible. In bHCRP group, Overall survival (OS) Mean (Standard Error) was 87(2) and 81(4) months for ≥ 50% vs < 50% CRP decrease respectively. In bNCRP group, OS was 90(3) and 105(3) months for ≥ 2x vs < 2x increase in CRP levels, respectively. These differences remained significant after adjusting for confounders.
Conclusion: After a baseline normal CRP an increase of 2-fold or greater was associated with clinical and statistically significantly shorter OS. Conversely, after a baseline high CRP a 50% or greater decrease from baseline was associated with longer OS. Quantification of clinically meaningful CRP change could impact more effective CRP use as a biomarker, prognostic indicator and aid therapeutic decision making. This is especially important to reduce healthcare disparities in financially struggling healthcare systems.

Keywords
C-Reactive Protein, solid tumors, biomarker, overall survival

Article Details

How to Cite
Lasheen, W., & Walsh, D. (2025). C-Reactive Protein in Solid Tumors: Clinically Meaningful Change. Current Cancer Reports, 7, 280-285. https://doi.org/10.25082/CCR.2025.01.003

References

  1. Sproston NR, Ashworth JJ. Role of C-Reactive Protein at Sites of Inflammation and Infection. Frontiers in Immunology. 2018, 9. https://doi.org/10.3389/fimmu.2018.00754
  2. Shine B, de Beer FC, Pepys MB. Solid phase radioimmunoassays for human C-reactive protein. Clinica Chimica Acta. 1981, 117(1): 13-23. https://doi.org/10.1016/0009-8981(81)90005-x
  3. MacGregor AJ, Gallimore JR, Spector TD, et al. Genetic Effects on Baseline Values of C-Reactive Protein and Serum Amyloid A Protein: A Comparison of Monozygotic and Dizygotic Twins. Clinical Chemistry. 2004, 50(1): 130-134. https://doi.org/10.1373/clinchem.2003.028258
  4. Albert MA, Glynn RJ, Buring J, et al. C-Reactive protein levels among women of various ethnic groups living in the United States (from the Women’s Health Study). The American Journal of Cardiology. 2004, 93(10): 1238-1242. https://doi.org/10.1016/j.amjcard.2004.01.067
  5. Carlson CS, Aldred SF, Lee PK, et al. Polymorphisms within the C-Reactive Protein (CRP) Promoter Region Are Associated with Plasma CRP Levels. The American Journal of Human Genetics. 2005, 77(1): 64-77. https://doi.org/10.1086/431366
  6. Heikkila K, Ebrahim S, Lawlor DA. A systematic review of the association between circulating concentrations of C reactive protein and cancer. Journal of Epidemiology & Community Health. 2007, 61(9): 824-833. https://doi.org/10.1136/jech.2006.051292
  7. Gabay C, Kushner I. Acute-Phase Proteins and Other Systemic Responses to Inflammation. Epstein FH, ed. New England Journal of Medicine. 1999, 340(6): 448-454. https://doi.org/10.1056/nejm199902113400607
  8. Ockene IS, Matthews CE, Rifai N, et al. Variability and Classification Accuracy of Serial High-Sensitivity C-Reactive Protein Measurements in Healthy Adults. Clinical Chemistry. 2001, 47(3): 444-450. https://doi.org/10.1093/clinchem/47.3.444
  9. Allin KH, Bojesen SE, Nordestgaard BG. Baseline C-Reactive Protein Is Associated With Incident Cancer and Survival in Patients With Cancer. Journal of Clinical Oncology. 2009, 27(13): 2217-2224. https://doi.org/10.1200/jco.2008.19.8440
  10. Chaturvedi AK, Caporaso NE, Katki HA, et al. C-Reactive Protein and Risk of Lung Cancer. Journal of Clinical Oncology. 2010, 28(16): 2719-2726. https://doi.org/10.1200/jco.2009.27.0454
  11. Feng Y, Wang J, Tan D, et al. Relationship between circulating inflammatory factors and glioma risk and prognosis: A meta‐analysis. Cancer Medicine. 2019, 8(17): 7454-7468. https://doi.org/10.1002/cam4.2585
  12. Guo L, Liu S, Zhang S, et al. C-reactive protein and risk of breast cancer: A systematic review and meta-analysis. Scientific Reports. 2015, 5(1). https://doi.org/10.1038/srep10508
  13. Zhou B, Shu B, Yang J, et al. C-reactive protein, interleukin-6 and the risk of colorectal cancer: a meta-analysis. Cancer Causes & Control. 2014, 25(10): 1397-1405. https://doi.org/10.1007/s10552-014-0445-8
  14. Shrotriya S, Walsh D, Nowacki AS, et al. Serum C-reactive protein is an important and powerful prognostic biomarker in most adult solid tumors. Ahmad A, ed. PLOS ONE. 2018, 13(8): e0202555. https://doi.org/10.1371/journal.pone.0202555
  15. McCall P, Catlow J, McArdle PA, et al. Tumoral C-reactive protein and nuclear factor kappa-B expression are associated with clinical outcome in patients with prostate cancer. Cancer Biomarkers. 2012, 10(2): 91-99. https://doi.org/10.3233/cbm-2012-0236
  16. Shrotriya S, Walsh D, Bennani-Baiti N, et al. C-Reactive Protein Is an Important Biomarker for Prognosis Tumor Recurrence and Treatment Response in Adult Solid Tumors: A Systematic Review. Zhang L, ed. PLOS ONE. 2015, 10(12): e0143080. https://doi.org/10.1371/journal.pone.0143080
  17. Lorton CM, Higgins L, O’Donoghue N, et al. C-Reactive Protein and C-Reactive Protein-Based Scores to Predict Survival in Esophageal and Junctional Adenocarcinoma: Systematic Review and Meta-Analysis. Annals of Surgical Oncology. 2021, 29(3): 1853-1865. https://doi.org/10.1245/s10434-021-10988-x
  18. Habibzadeh F, Habibzadeh P, Yadollahie M. On determining the most appropriate test cut-off value: the case of tests with continuous results. Biochemia Medica. Published online 2016: 297-307. https://doi.org/10.11613/bm.2016.034
  19. Ko YJ, Abdelsalam M, Kavan P, et al. What Is a Clinically Meaningful Survival Benefit in Refractory Metastatic Colorectal Cancer? Current Oncology. 2019, 26(2): 255-259. https://doi.org/10.3747/co.26.4753