Emerging markers of cancer cachexia and their relationship to sarcopenia

Abstract

Purpose Emerging biomarkers of cancer cachexia and their roles in sarcopenia and prognosis are poorly understood. Baseline assessments of anthropometrics, sarcopenia, cachexia status and biomarkers of cachexia were measured in patients with advanced cancer and healthy controls. Thereafter, relationships of the biomarkers with cachexia and sarcopenia were explored. Methods A prospective case–control design was used, including 40 patients with advanced cancer and 40 gender, age-matched controls. Bioelectrical impedance [skeletal muscle index (SMI)] and hand dynamometry [hand grip strength (HGS)] assessed sarcopenia and a validated tool classified cancer cachexia. Albumin, lymphocyte and platelet counts, haemoglobin, C-reactive protein (CRP), pro-inflammatory cytokines/chemokines and citrullinated histone H3 (H3Cit) were measured. Results Patients had significantly lower SMI (6.67 kg/m2 versus 7.67 kg/m2, p = < 0.01) and HGS (24.42 kg versus 29.62 kg) compared to controls, with 43% being sarcopenic. Significant differences were found for albumin, lymphocyte and platelet counts, haemoglobin, CRP, and tumour necrosis factor α (TNFα), (p < 0.01). Interleukin (IL)-6 (p < 0.04), IL-8 (p = 0.02), neutrophil/lymphocyte ratio (NLR), p = 0.02, platelet/lymphocyte (PLR) ratio, p < 0.01 and systemic immune inflammatory index (SII), p < 0.01 differed significantly. No difference was observed for CXC motif chemokine ligand 5 [CXCL5 or epithelial neutrophil-activating peptide 78 (ENA78)] or H3Cit. Albumin and haemoglobin correlated negatively with total protein, skeletal muscle mass and SMI (all p < 0.01). The presence of sarcopenia associated significantly with albumin, haemoglobin and CRP. Conclusion Significant relationships and differences of haemoglobin, CRP and albumin supports future use of these biomarkers in cancer cachexia. CXCL5 and H3Cit as valuable biomarkers in cancer cachexia remains to be defined.

Relationships of emerging biomarkers of cancer cachexia with quality of life, appetite, and cachexia

“…In contrast to other studies, that showed more than a threefold increase of serum CXCL5 concentrations in cancer [ 17 ], the current study found no difference for cases vs. controls for CXCL5 ( p = 0.22) [ 19 ]. Studies that report raised CXCL5 levels may be questionable due to inconsistencies in CXCL5 measurement, differing primary diagnoses [ 17 ] and the degree of metastatic spread [ 35 ], factors that may have influenced CXCL5 results in the study by Lipshitz et al [ 19 ].…”

“…As described previously [ 19 ], measurement of systemic biomarker concentrations revealed statistically significant increases ( p < 0.05) in all of the following biomarkers in the group of cancer patients relative to controls: blood platelets, NLR, PLR, SII, CRP, IL-6, IL-8, and TNFα. Concentrations of biomarkers that were significantly decreased ( p < 0.05) in the cohort of cancer patients included albumin, Hb, and lymphocyte count, while white blood cell counts (WBCs), neutrophil counts, and concentrations of CXCL5 and H3Cit were comparable between patients and controls.…”

“…Baseline blood analyses showed that routine hematological and blood chemistry markers, cytokines, and biomarkers of inflammation were significantly different between cases and controls [ 19 ]. Hypoalbuminemia has been reported to have a direct impact on caregiver burden and is closely linked to a compromised QoL [ 32 ].…”

“…Significant differences were found between cases and controls for lymphocytes, platelets, NLR, PLR, and SII, and further significance was evident when comparing the mean values to the ROC curve analysis reference values. Additionally, CRP, TNFα, IL-6, and IL-8 were significantly elevated in the cases [ 19 ]. Importantly, research into the association of IL-8 with distant metastases, tumor progression, and tumor stage renders IL-8 useful as a diagnostic tool to determine the progression status of cancer.…”

“…Biomarker analyses were performed on the same cohort of cancer patients and healthy control individuals as reported previously [ 19 ]. Biomarkers investigated included serum albumin, Hb, neutrophils, lymphocytes, platelets and the investigational markers C-reactive protein (CRP), interleukin (IL)-6, IL-8, TNFα, H3Cit, and CXCL5.…”