Preoperative anemia in colorectal cancer: relationships with tumor characteristics, systemic inflammation, and survival

Abstract

Anemia is common in colorectal cancer (CRC) but its relationships with tumor characteristics, systemic inflammation, and survival have not been well characterized. In this study, blood hemoglobin levels and erythrocyte mean corpuscular volume (MCV) levels were measured in two independent cohorts of 148 CRC patients and 208 CRC patients, and their correlation with patient and tumor characteristics, systemic inflammatory markers (modified Glasgow Prognostic Score: mGPS; serum levels of thirteen cytokines, C-reactive protein, albumin), and survival were analyzed. We found that anemia, most frequently normocytic, followed by microcytic, was present in 43% of the patients. Microcytic anemia was most commonly associated with proximal colon tumor location. Average MCV and blood hemoglobin levels were lower in tumors with high T-class. Low blood hemoglobin associated with systemic inflammation, including high mGPS and high serum levels of C-reactive protein and IL-8. Particularly, normocytic anemia associated with higher mGPS. Normocytic anemia associated with a tendency towards worse overall survival (multivariate hazard ratio 1.61, 95% confidence interval 1.07-2.42, p = 0.023; borderline statistical significance considering multiple hypothesis testing). In conclusion, anemia in CRC patients is most frequently normocytic. Proximal tumor location is associated with predominantly microcytic anemia and systemic inflammation is associated with normocytic anemia.

Figure 1

Correlation between tumor location and blood hemoglobin levels (a) and erythrocyte mean corpuscular volume (MCV) levels (b) in the combined colorectal cancer cohort (n = 356). Utilizing CT colonography data, tumor location was coded into an estimation of tumor distance from anus. This estimation had linear negative correlation with blood hemoglobin levels and erythrocyte MCV levels.

Figure 2

2D visualization of the relationships between blood hemoglobin (Hb), serum C-reactive protein (CRP) levels, serum albumin levels, and serum cytokine levels in Cohort 1. The edges (connecting lines) depict the associations between the variables (only those with p < 0.0015 shown). The edge length illustrates the significance of the association. The correlations between Hb and other variables are represented by green (positive correlation) and red (negative correlation) edges, with the label indicating corresponding Pearson r for the correlation. The other associations are indicated by the grey edges. The 2D visualization was created with Cytoscape software platform, utilizing the Prefuse force directed algorithm weighted by the statistical significances of the correlations between individual variables. Abbreviations: CCL: Chemokine (C-C motif) ligand; CRP: C-reactive protein; CXCL: Chemokine (C-X-C motif) ligand; Hb: Hemoglobin; IFN: interferon IL: interleukin; PDGF: Platelet-derived growth factor.