Background Malnutrition and cachexia are frequent among head and neck cancer (HNC) patients and these syndromes are associated with both poor quality of life and unfavorable disease prognosis. Unfortunately, there are still no established biomarkers that could predict the development of cachexia. Among potential molecular alterations related to cancer cachexia, there are single-nucleotide polymorphisms (SNPs) within genes encoding pro-inflammatory cytokines such as TNF-α. The aim of the study To investigate TNF-α −1031T/C SNP as a risk factor of cachexia in 62 HNC patients subjected to radiotherapy. DNA was isolated from whole blood samples and genotyping was conducted using real-time PCR method by means of TaqMan SNP Genotyping Assay. TNF-alpha Human ELISA Kit was used to determine TNF-α concentration in each extracted plasma sample. Moreover, the relationship between genotype variants of TNF-α and plasma level of TNF-α was examined. Detailed clinical–demographic and nutritional data were collected from each study participant. Results CC genotype carriers were at a significantly higher risk of being qualified as cachectic compared with other genotype carriers (p = 0.044; HR = 3.724). Subjects, who carried CC genotype had significantly lower body mass compared to patients with TT and CT genotype (p = 0.045). Moreover, CC individuals had the highest TNF-α plasma level (median 10.70 ± 0.72 pg/mL, p = 0.006) among the studied cases. We also noted, that CC genotype carriers had significantly higher risk of early death incidence compared to other genotype carriers [overall survival (OS): 28 vs 38 months (HR = 3.630, p = 0.013)]. Conclusion Despite the differences between SGA and NRS scoring, the presence of CC genotype could be a useful objective marker allowing for the prediction of cachexia development in both parenterally nourished and non-parenterally nourished patients. Patients with CC genotype had also the highest risk of early death incidence; therefore, such individuals should be qualified for parenteral nutrition and supportive care at the time of diagnosis to improve further therapy outcomes. Moreover, this is the first study demonstrating the relationship between TNF-α −1031T/C polymorphism and plasma level of TNF-α. This is also the first paper investigating the role of TNF-α −1031T/C in cancer cachexia.

(1) Introduction: Autoimmune hepatitis (AIH) is a chronic disease. A persistent autoimmune reaction in the liver is significantly related to the systemic inflammatory response. Extended Inflammation Parameters (EIP) can be used to assess the activation of immune cells such as activated neutrophils (NEUT-RI and NEUT-GI) and activated lymphocytes (RE-LYMP and AS-LYMP) in the phase of active inflammation. The role of the systemic inflammatory response markers should also be emphasised, especially: NLR, PLR, and RLR, which have recently been widely studied as markers in autoimmune skin diseases or liver diseases. (2) Materials and Methods: The study included 30 patients with AIH and 30 healthy volunteers. The parameters of the EIP group (RE-LYMP, AS-LYMP, NEUT-RI, NEUT-GI), calculated haematological indices Red Blood Cell Distribution Width-to-Platelet Ratio (RPR), Mean Platelet Volume-to-Platelet Ratio (MPR), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Red Blood Cell Distribution Width-to-Lymphocyte Ratio (RLR), and selected blood morphological and biochemical indices were analysed. The aim of the study was to assess the usefulness of the EIP and systemic inflammatory response markers in the diagnostics of AIH. (3) Results: Compared to the controls, the patients with AIH showed significantly higher EIP values: NEUT-RI (48.05 vs. 43.30), NEUT-GI (152.65 vs. 147.40), RE-LYMP (0.07 vs. 0.03), and the inflammatory response markers: MPR (0.05 vs. 0.04), RPR (0.07 vs. 0.05), and NLR (2.81 vs. 1.42. Among the examined markers, EIP has significant diagnostic potential: NEUT-RI (AUC = 0.86), NEUT-GI (AUC = 0.80), and RE-LYMP (AUC = 0.78), and so do calculated haematological indices, i.e., MPR (AUC = 0.75), PLR (AUC = 1.00), and RLR (AUC = 1.00) Moreover, the importance of NEUT-GI (AUC = 0.89), MPR (AUC = 0.93), PLR (AUC = 0.86), RPR (AUC = 0.91), and FIB-4 (AUC = 0.83) in the detection of liver fibrosis in the course of AIH has also been proven. (4) Conclusions: EIP and systemic inflammatory response markers may turn out to be useful in detecting AIH and in looking for features of already developed liver cirrhosis in its course.

Background: Cachexia is an unfavorable metabolic syndrome causing involuntary weight loss followed by muscle wasting, which can lead to the exacerbation of chronic heart failure (CHF), and considerably increases mortality rate among CHF patients. Unfortunately, until now it has not been possible to determine factors that could improve clinical options for cachexia management or enable the identification of patients at risk of its development. We assessed how cachexia conditions in CHF reflect cardiac and laboratory parameters in comparison with non-cachectic patients. Methods: 66 women were enrolled to the study group and underwent meticulous screening, according to recent clinical guidelines, in order to enable CHF and cachexia detection. Body composition was evaluated by bioelectrical impedance analysis (BIA) and laboratory tests were supplemented by analysis of plasma circulating irisin. Results: A negative correlation between irisin concentration and both CRP and TNF-α was recorded (R = −0.362 and R = −0.243; p < 0.05). Irisin concentration positively correlated with EF% (R = 0.253; p = 0.046) and negatively with LVESd, LVEDd and NT-proBNP (R = −0.326, −0.272, and −0.320; p < 0.05). Both low levels of circulating irisin and Capacitance of membrane (Cm) were selected as unfavorable factors affecting cachexia in CHF patients (OR = 1.39 and 34.49; p < 0.05). Combination of Cm, irisin, CRP and albumin demonstrated sensitivity of 93.3% and specificity of 85.3% (AUC = 0.949) for distinguishing between cachectic and non-cachectic CHF patients. Conclusions: Selected parameters reliably reflect cachectic conditions in CHF, and the proposed approach for cachexia based on the combined analysis of at least a few non-invasive markers could offer new opportunities for improving clinical outcomes in CHF patients.

Background: Muscle atrophy is a complex catabolic condition developing under different inflammatory-related systemic diseases resulting in wasting of muscle tissue. While the knowledge of the molecular background of muscle atrophy has developed in recent years, how the atrophic conditions affect the long non-coding RNA (lncRNAs) machinery and the exact participation of the latter in the mediation of muscle loss are still unknown. The purpose of the study was to assess how inflammatory condition developing under the tumor necrosis factor alpha (TNF-α) treatment affects the lncRNAs’ expression in a mouse skeletal muscle cell line. Materials and method: A C2C12 mouse myoblast cell line was treated with TNF-α to develop atrophy, and inflammatory-related lncRNAs mediating muscle loss were identified. Bioinformatics was used to validate and analyze the discovered lncRNAs. The differences in their expression under different TNF-α concentrations and treatment times were investigated. Results: Five lncRNAs were identified in a discovery set as atrophy related and then validated. Three lncRNAs, Gm4117, Ccdc41os1, and 5830418P13Rik, were selected as being significant for inflammatory-related myotube atrophy. Dynamics changes in the expression of lncRNAs depended on both TNF-α concentration and treatment time. Bioinformatics analysis revealed the mRNA and miRNA target for selected lncRNAs and their putative involvement in the molecular processes related to muscle atrophy. Conclusions: The inflammatory condition developing in the myotube under the TNF-α treatment affects the alteration of lncRNAs’ expression pattern. Experimental and bioinformatics testing suggested the prospective role of lncRNAs in the mediation of muscle loss under an inflammatory state.

Background: Investigation of novel cachexia-related markers is one of the major challenges in contemporary oncology. Among studied markers, the miRNA seems to be promising due to its possibility to regulate genes responsible for induction of inflammatory response, muscle atrophy and fat tissue wasting. The aim of the study was to investigate the role of blood-circulating miRNA-130a in prediction of cancer cachexia in 70 head and neck cancer patients (HNC) subjected to radiotherapy. Moreover, diagnostic accuracy of SGA (Subjective Global Assessment) scoring and miRNA-130a level was evaluated in various cachexia models. Results: miRNA-130a level negatively correlated with plasma TNF-α concentration (r = −0.560; p < 0.001). Patients with low miRNA expression had over 3-fold higher risk of body mass index (BMI) decrease below 18.5 after the termination of therapy; over 6-fold higher risk of losing over 5% of body weight and higher risk of >10% weight reduction odds ratio (OR) = 14.18 compared to other cases. ROC analysis performed for miRNA-130a allowed to distinguish cachectic patients (body weight loss >5%) from moderately or mildly malnourished ones with optimal sensitivity of 79.4% and specificity of 80.8% area under the curve (AUC) = 0.865). miRNA significantly improved nutritional assessment conducted using SGA, achieving the following values: sensitivity 88.6%, specificity 94.3%, positive predictive value (PPV) 93.9%, negative predictive value (NPV).89.2%. Conclusion: miRNA-130a demonstrates potential clinical utility in prediction of cachexia prior to the therapy in HNC patients. Simultaneous use of both tools—SGA and miRNA—significantly improved the accuracy in the diagnosis of cachexia.