1. Emerging Biomarkers of Cancer Cachexia and their Relationship to Sarcopenia

 

Sarcopenia assessment using skeletal muscle index (SMI), handgrip strength (HGS) and biomarkers [albumin, haemoglobin (Hb), neutrophils, lymphocytes, platelets, CRP, TNFα, IL-6, IL-8, C-X-C motif chemokine ligand 5 (CXCL5) and citrullinated histone H3 (H3Cit)] were compared for 40 cases (advanced cancer) and 40 healthy controls. Baseline differences, relationships and correlations were explored for significance of biomarkers to sarcopenia.

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SMI and HGS were measured in a prospective case-control, age and gender matched study with bioelectrical impedance and hand dynamometry. A validated cachexia staging tool was utilized for classification. Routine or assay-specific kits were used for biomarker analysis. Summary and descriptive statistics, and regression analyses for correlations were undertaken. ROC curve analysis was used to define “normal” values of biomarkers. P<0.05 defined statistical significance.

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Mean SMI for cases was 6.67kg/m2 and controls 7.67kg/m2, p=<0.01. Mean HGS was 24.42kg (cases) and 29.62kg (controls), p=0.01. Sarcopenia presence was 43% and 60% SMI or HGS cut-offs respectively. There were significant differences for albumin, lymphocytes, platelets, Hb, PLR, SII, CRP, TNFα, all at p<0.01, NLR (p=0.02), IL-6 (p<0.04) and IL-8 (p=0.02) between cases and controls. No significance was found for CXCL5 (p=0.22) or H3Cit (p=0.99) between groups. Albumin and Hb correlated negatively with SMI (p<0.01) and albumin, Hb, CRP (p<0.01) and TNFα (p=0.04) were significantly related to sarcopenia. HGS measurements correlated significantly to albumin (r=0.45, p<0.01) and Hb, (r=0.44, p<0.001) and for sarcopenia, HGS correlated significantly to PLR, TNFα, IL-6 and CRP.

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CXCL5 and H3Cit were not reliable biomarkers for cancer cachexia and were not significantly related to sarcopenia. CRP, albumin and Hb demonstrated significant differences between cases and controls, and relationships and correlations to sarcopenia.

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2. Relationships of Emerging Biomarkers of Cancer Cachexia to Quality of Life and Appetite

 

Rationale: Quality of Life (QoL), appetite and biomarkers [albumin, haemoglobin (Hb), neutrophils, lymphocytes, platelets, CRP, TNFα, IL-6, IL-8, C-X-C motif chemokine ligand5 (CXCL5) and citrullinated histoneH3 (H3Cit)] were compared for 40 cases with advanced cancer and 40 healthy controls. Significance for baseline differences, relationships and correlations were explored for biomarkers to QoL and appetite.

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Methods: In a prospective case-control, age and gender matched study EORTC-QLQ-C30 and FAACT A/CS-12 were used to assess QoL and appetite. Routine or assay-specific kits were used for biomarker analysis. Summary and descriptive statistics, and regression analyses for correlations were undertaken. P<0.05 defined statistical significance.

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Results: Global Health Status (QL-G), functional scales (QL-FS) and symptom scales (QL-SS) differed for cases and controls (p<0.01). For cases, significance was p<0.01, p<0.01 and p=0.01 for QL-G, QL-FS and QL-SS to references values. Appetite scores were -12.58 for cases and 6.08 for controls, p<0.01 and 30% of cases scored “poor” appetites. Albumin, lymphocytes, platelets, Hb, PLR, SII, CRP, TNFα, all at p<0.01, NLR (p=0.02), IL-6 (p<0.04) and IL-8 (p=0.02) differed significantly between cases and controls. No difference was found for CXCL5 (p=0.22) or H3Cit (p=0.99). Albumin, NLR, Hb, PLR, SII, TNFα, IL-8 and CRP showed significant correlations to all QoL aspects. QL-FS correlated significantly to CXCL5 (p=0.04) using categories. Significant associations for FAACT A/CS-12 were: NLR (p=0.002), Hb (p<0.001) and PLR (p<0.01). For categorized appetite scores albumin (p=0.03) and CRP (p=0.002) were significant.   

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Conclusion: CXCL5 and H3Cit were not reliable biomarkers for cancer cachexia and were not significantly related to QoL and appetite. Albumin, NLR, Hb, PLR, SII, TNFα, IL-8 and CRP were reliable indicators for QoL and appetite.