Combined C-Reactive Protein and Novel Inflammatory Parameters as a Predictor in Cancer—What Can We Learn from the Hematological Experience?

Abstract

The acute phase reaction is a systemic response to acute or chronic inflammation. The serum level of C-reactive protein (CRP) is the only acute phase biomarker widely used in routine clinical practice, including its uses for prognostics and therapy monitoring in cancer patients. Although Interleukin 6 (IL6) is a main trigger of the acute phase reactions, a series of acute phase reactants can contribute (e.g., other members in IL6 family or IL1 subfamily, and tumor necrosis factor α). However, the experience from patients receiving intensive chemotherapy for hematological malignancies has shown that, besides CRP, other biomarkers (e.g., cytokines, soluble cytokine receptors, soluble adhesion molecules) also have altered systemic levels as a part of the acute phase reaction in these immunocompromised patients. Furthermore, CRP and white blood cell counts can serve as a dual prognostic predictor in solid tumors and hematological malignancies. Recent studies also suggest that biomarker profiles as well as alternative inflammatory mediators should be further developed to optimize the predictive utility in cancer patients. Finally, the experience from allogeneic stem cell transplantation suggests that selected acute phase reactants together with specific markers of organ damages are useful for predicting or diagnosing graft versus host disease. Acute phase proteins may also be useful to identify patients (at risk of) developing severe immune-mediated toxicity after anticancer immunotherapy. To conclude, future studies of acute phase predictors in human malignancies should not only investigate the conventional inflammatory mediators (e.g., CRP, white blood cell counts) but also combinations of novel inflammatory parameters with specific markers of organ damages.

The Biological Context of C-Reactive Protein as a Prognostic Marker in Renal Cell Carcinoma: Studies on the Acute Phase Cytokine Profile

“…We cannot exclude the possibility that inflammaging (i.e., inflammation associated with aging, see [ 50 ]) or other chronic inflammatory diseases contributed to the observed acute phase reaction. However, we did not perform any additional selection of patients included in our present cytokine studies.…”

The Acute Phase Reaction and Its Prognostic Impact in Patients with Head and Neck Squamous Cell Carcinoma: Single Biomarkers Including C-Reactive Protein Versus Biomarker Profiles

“…Inflammatory parameters are considered as possible prognostic markers in several human malignancies [ 9 , 55 ]. These parameters include both acute phase proteins and peripheral blood concentrations of various leukocyte subsets and platelets [ 62 , 72 , 73 , 74 , 75 ]. Increased leukocyte and platelet counts were also seen for several of our HNSCC patients, and we observed significant correlations between IL6 levels, WBC counts, and CRP levels.…”

“…Further studies including a larger number of patients and alternative mediator combinations should therefore be encouraged to verify our present results and to identify the optimal combination of mediators for prognostication. Systemic levels of inflammatory mediators have been included in prognostic indices together with other (e.g., clinical) parameters for various inflammatory conditions, including malignant diseases [ 62 ]. Our present study and our ROC analyses suggest that relevant cut-off levels can be identified and can then be used to design a prognostic index for patients with HPV-negative HNSCC, but the number of patients in our present study is too low to allow a suggestion of the exact cut-off values to be used in such a prognostic index.…”

“…Cluster data are explained in the lower part of the figure. The isolated middle column indicates patient state by the end of the study; still alive (blue), dead from HNSCC (green) or other cause (red), and further complementary information including available histopathological findings, as well as inflammatory markers [ 62 ]. The number of patients in each of the three main clusters are indicated to the right.…”

The Implementation of Mass Spectrometry-Based Proteomics Workflows in Clinical Routines of Acute Myeloid Leukemia: Applicability and Perspectives

“…Several studies of patients with various malignancies have shown that the acute phase reaction, i.e., systemic inflammatory responses, have an adverse prognostic impact in several malignancies, including certain hematological malignancies [ 66 ]. However, systemic inflammatory activity has not been used for prognostication in human AML.…”