Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer

Abstract

In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin‐3, mannose‐binding lectin, ficolin‐1, ficolin‐2 and ficolin‐3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer in patients with NSSC. Patients were included from the DOC, Department of Infectious Diseases, Copenhagen University Hospital Hvidovre. Patients were given a final diagnosis based on the combined results from scans, blood work and physical examination. Weight loss, Charlson score and previous cancer were registered on admission, and plasma concentrations of biomarkers were measured. The primary outcome was incident cancer within 1 year. Out of 197 patients included, 39 patients (19.8%) were diagnosed with cancer. Patients with cancer were significantly older and had a higher burden of comorbidities and previous cancer diagnoses compared to patients who were not diagnosed with cancer. Previous cancer, C‐reactive protein (CRP) and suPAR were significantly associated with newly diagnosed cancer during follow‐up in multiple logistic regression analyses adjusted for age, sex and CRP. Neither any of the PRRs investigated nor self‐reported weight loss was associated with cancer. In this study, previous cancer, CRP and suPAR were significantly associated with cancer diagnosis in patients with NSSC. Ficolin‐1‐3, MBL and pentraxin‐3 were not associated with cancer.

Assessment of tumor-induced pain and C-reactive protein levels in dogs with canine transmissible venereal tumors

“…The normal values are indicative of the absence of any discrepancy in hematopoietic as well as in immune functioning (18). The findings are in accordance with previous studies conducted to find the association between elevated levels of biomarkers and several organ-specific malignancies (26)(27)(28). Proteins (matrix metalloproteinase-7 and matrix metalloproteinase-12) are generally related to tumor growth and contribute to sustained proliferation and invasion.…”

“…Proteins (matrix metalloproteinase-7 and matrix metalloproteinase-12) are generally related to tumor growth and contribute to sustained proliferation and invasion. CRP has been extensively studied as a biomarker of malignancies (26,29) and is supposed to support the tumor microenvironment by inducing tumor-promoting inflammation (30). Similarly, in canines, elevated levels of CRP have consistently been attributed to increased tumor progression and poor prognosis (31).…”

Remote ischemic preconditioning does not influence lectin pathway protein levels in head and neck cancer patients undergoing surgery

“…M-ficolin is produced by PLOS ONE neutrophils and monocytes [45] and increased levels might therefore suggest ongoing inflammation. MBL and MASP-2 concentrations did not differ between cancer patients and healthy individuals, which is in accordance with previous studies by Rasmussen et al and Swierzko et al [43,46,47]. However, other previous studies reported increased concentrations of MBL and MASP-2 and increased MBL/MASP activity in cancer patients [12,13,31,48].…”

“…A previous study found threefold increases in H-ficolin levels in ovarian cancer patients suggesting this protein could be a potential biomarker for cancer [42]. However, a recent study by Rasmussen et al did not find increased H-ficolin levels in patients with various types of cancer [43]. The decrease in MAp44 in the present study is consistent with earlier findings in colorectal cancer patients [14].…”

Prognostic Value of the Glasgow Prognostic Score or Modified Glasgow Prognostic Score for Patients with Colorectal Cancer Receiving Various Treatments: a Systematic Review and Meta-Analysis

“…Additionally, CRP is associated with the activity of infiltrated immune cells, including dendritic cells, T cells, and natural killer cells [72,73]. Many studies have shown that CRP is an independent biomarker for predicting prognostic outcome in various cancers [74][75][76]. The serum albumin level is used as a biomarker to evaluate liver function and nutritional status.…”