BackgroundMalnutrition 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 studyTo 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.ResultsCC 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)].ConclusionDespite 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.

Malnutrition, which can be determined by subjective and objective methods, has a high prevalence in head and neck cancer patients. Subjective Global Assessment is a subjective method of nutritional status evaluation. Phase angle, determined by bioelectrical impedance analysis, is proposed as an objective nutritional marker in various disease conditions. The study was conducted to investigate the association between phase angle and Subjective Global Assessment to validate the determination of the nutrition status in adult patients with head and neck cancer. In a prospective cohort study, patients were classified as either well-nourished or malnourished using the Subjective Global Assessment. Phase angle measured by bioelectrical impedance analysis was planned in 75 naive patients with histologically confirmed head and neck cancer. Receiver operating characteristic curves were estimated using the non-parametric method to determine the optimal cut-off level of phase angle. The study was conducted on a cohort population of 75 patients. Well-nourished patients (n = 45) had a statistically significantly higher (p = 0.005) median phase angle score (5.25º) as compared to those who were malnourished (4.73º) (n = 30). A phase angle cut-off of 4.73 was 80 % sensitive and 56.7 % specific in detecting malnutrition diagnosed by SGA in these populations. Phase angle is considered to be a nutritional indicator in patients with head and neck cancer in detecting malnutrition. Further observations are needed to calculate survival, and validate the prognostic significance of phase angle. For future studies, it is important to indicate the specificity of the PA in comparison to SGA measurement.

Selected SNPs of genes encoding DNA repair enzymes and cell division regulation proteins could be useful biomarkers for prediction of platinum and vinorelbine-based chemotherapy toxicity in patients with advanced NSCLC.

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.

In response to various stimuli, neutrophils and eosinophils can release neutrophil extracellular traps (NET) consisting of proteolytic enzymes, DNA and other components of the cell nucleus. The NETosis process has been characterized as a mechanism of programmed cell death, which leads to chromatin decondensation and disintegration of organelles, followed by lysis of the cell membrane. In recent years the significant role of neutrophils in the pathogenesis of cancer has been highlighted. The presence of two subpopulations of TAN with different phenotypes and functions - acting antitumor "N1" and the pro-cancerous "N2" - has been discovered. By the release of cytokines and chemokines neutrophils may affect angiogenesis and contribute to escape of tumor cells from immune surveillance. Interactions between cells and the microenvironment are of vital importance both for the preservation of homeostasis in normal tissue and tumor growth. They affect the initiation of disease progression and prognosis. The impact of NETosis on the process of metastasis is evaluated in the context of the functions of the individual components of the NET (MMP-9, CG, NE). Furthermore, presumably the pro- or anti-tumor effect of NETosis depends on many factors including the status of the immune system or tumor microenvironment. Probably the cancer cells can be captured by the NET microenvironment in the same manner as microorganisms. However, the high concentration of proteins released during NETosis can induce their proliferation and inhibit apoptosis, thus promoting tumor growth. A better understanding of NETosis function in tumor progression may lead to the emergence of new prognostic factors and targets for therapy in many types of cancer.