CRP and colorectal cancer

C-reactive protein (CRP), a representative marker for inflammation, is known for its association with disease progression in many cancer types (1)

• CRP reflects inflammatory status and is a component of the inflammatory response of the immune system
  
  
• CRP level and risk of colorectal cancer (CRC)
  • several studies have reported that in occurrence, progression, metastasis, and recurrence of colorectal cancer, systemic inflammation has an important role, and that CRP may be a useful indicator of inflammatory response (2,3)
    • results from various studies have proven that precancerous lesions are derived from systemic inflammation and local inflammation of the mucous membrane as part of the process of cell degeneration, and that colorectal cancer (CRC) progresses from adenoma to adenocarcinoma
  • been reported that colorectal cancer patients had a significantly higher level of CRP in preoperative blood compared with healthy controls (1)
  • a study in Chinese men showed that (4):
    • circulating CRP level is positively associated with CRC risk in Chinese men, and this association, at least in part, is explained by inflammation-related cancerous or precancerous processes
  • Jung et al found evidence of the possible use of CRP as a CRC-predictive biomarker in women with particular behaviors and CRP marker-informed interventions to reduce CRC risk
    
    
• assessment of CRC risk related to adenomas
  • high CRP level is associated with high-risk adenoma in both men and women (6)

Notes:

• cancer disease describes any pathology involving uncontrolled cell growth
  • as cells duplicate, they can remain localized in defined tissues, forming tumor masses and altering their microenvironmental niche, or they can disseminate throughout the body in a metastatic process affecting multiple tissues and organs
  • as tumors grow and metastasize, they affect normal tissue integrity and homeostasis which signals the body to trigger the acute phase inflammatory response
    • CRP is a predominant protein of the acute phase response
      • its blood levels have long been used as a minimally invasive index of any ongoing inflammatory response, including that occurring in cancer
      • half-life is 19 hours in both health and disease (8)
        • CRP secretion by hepatocytes appears controlled by interleukin 6 (IL-6)
        • interleukin-1 (IL-1) and tumor necrosis factor (TNF) also stimulate CRP synthesis
        • CRP is a stable downstream marker of inflammation, unlike the pro-inflammatory cytokines, which have short half-lives (minutes)
      • CRP exists in multiple isoforms with distinct biological activities (7)
        • CRP in its monomeric, modified isoform (mCRP)
          • modulates inflammatory responses by inserting into activated cell membranes and stimulating platelet and leukocyte responses associated with acute phase responses to tumor growth
          • also binds components of the extracellular matrix in involved tissues
        • CRP in its pentameric isoform (pCRP)
          • is the form quantified in diagnostic measurements of CRP, is notably less bioactive with weak anti-inflammatory bioactivity
          • its accumulation in blood is associated with a continuous, low-level inflammatory response and is indicative of unresolved and advancing disease, as occurs in cancer
        • note though that CRP is a non-specific marker
          • levels can rise for numerous reasons independent of the cancer; this also reduces the value of single versus serial CRP measurements
      • a high CRP was associated with higher mortality in 90% of reports in people with solid tumors primary sites (8)
        • particularly notable in GI malignancies and kidney malignancies
        • in other solid tumors (lung, pancreas, hepatocellular cancer, and bladder) an elevated CRP also predicted prognosis
        • also evidence to support the use of CRP to help decide treatment response and identify tumor recurrence

Reference:

• Kwon K.A., et al. Clinical significance of preoperative serum vascular endothelial growth factor, interleukin-6, and C-reactive protein level in colorectal cancer. BMC Cancer 2010; 10: 203.
• Law DJ, Olschwang S, Monpezat JP, Lefrancois D, Jagelman D, Petrelli NJ, Thomas G, Feinberg AP. Concerted nonsyntenic allelic loss in human colorectal carcinoma. Science. 1988;241(4868):961-965. doi: 10.1126/science.2841761.
• Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988;319(9):525–532
• Wu J, Cai Q, Li H, et al. Circulating C-reactive protein and colorectal cancer risk: a report from the Shanghai Men's Health Study. Carcinogenesis. 2013;34(12):2799-2803. doi:10.1093/carcin/bgt288
• Jung SY, Yu H, Pellegrini M, Papp JC, Sobel EM, Zhang ZF. Genetically determined elevated C-reactive protein associated with primary colorectal cancer risk: Mendelian randomization with lifestyle interactions. Am J Cancer Res. 2021;11(4):1733-1753. Published 2021 Apr 15.
• Lee HM, Cha JM, Lee JL, Jeon JW, Shin HP, Joo KR, Yoon JY, Lee JI. High C-reactive protein level is associated with high-risk adenoma. Intest Res. 2017 Oct;15(4):511-517. doi: 10.5217/ir.2017.15.4.511. Epub 2017 Oct 23. PMID: 29142519; PMCID: PMC5683982.
• Hart PC, Rajab IM, Alebraheem M, Potempa LA. C-Reactive Protein and Cancer-Diagnostic and Therapeutic Insights. Front Immunol. 2020;11:595835. Published 2020 Nov 19. doi:10.3389/fimmu.2020.595835
• Shrotriya S, Walsh D, Bennani-Baiti N, Thomas S, Lorton C. C-Reactive Protein Is an Important Biomarker for Prognosis Tumor Recurrence and Treatment Response in Adult Solid Tumors: A Systematic Review. PLoS One. 2015;10(12):e0143080. Published 2015 Dec 30. doi:10.1371/journal.pone.0143080