Morphofunctional and Molecular Assessment of Nutritional Status in Head and Neck Cancer Patients Undergoing Systemic Treatment: Role of Inflammasome in Clinical Nutrition.

Soraya León-Idougourram,Fernando L-López,Natalia Herman-Sánchez,María Ángeles Gálvez Moreno,Manuel D Gahete,Concepción Muñoz Jiménez,María José Molina Puertas,Raúl M Luque,Gregorio Manzano García,Rosario Alonso-Echague,Alfonso Calañas Continente,Jesús M Pérez-Gómez,Aura D Herrera-Martínez

doi:10.3390/cancers14030494

Abstract

Simple SummaryMalnutrition in patients with head and neck cancer is associated with worse clinical evolution and prognosis. Accurate nutritional assessments allow for early-identification of patients at risk of malnutrition. We aimed to perform a novel morphofunctional nutritional evaluation, including molecular analysis in patients with head and neck cancer who are undergoing systemic treatment. A morphofunctional nutritional assessment includes bioimpedance, anthropometric, ultrasound and biochemical measurements. We observed that malnutrition induces a profound alteration in the gene-expression pattern of inflammasome-machinery components, which are related with clinical nutritional parameters. This molecular analysis should be further studied as potential targets for nutrition-focused treatment strategies in cancer patients.Malnutrition in patients with head and neck cancer is frequent, multifactorial and widely associated with clinical evolution and prognosis. Accurate nutritional assessments allow for early identification of patients at risk of malnutrition in order to start nutritional support and prevent sarcopenia. We aimed to perform a novel morphofunctional nutritional evaluation and explore changes in inflammasome-machinery components in 45 patients with head and neck cancer who are undergoing systemic treatment. To this aim, an epidemiological/clinical/anthropometric/biochemical evaluation was performed. Serum RCP, IL6 and molecular expression of inflammasome-components and inflammatory-associated factors (NOD-like-receptors, inflammasome-activation-components, cytokines and inflammation/apoptosis-related components, cell-cycle and DNA-damage regulators) were evaluated in peripheral-blood mononuclear-cells (PBMCs). Clinical-molecular correlations/associations were analyzed. Coherent and complementary information was obtained in the morphofunctional nutritional assessment of the patients when bioimpedance, anthropometric and ultrasound data were analyzed. These factors were also correlated with different biochemical and molecular parameters, revealing the complementary aspect of the whole evaluation. Serum reactive C protein (RCP) and IL6 were the most reliable parameters for determining patients with decreased standardized phase angle, which is associated with increased mortality in patients with solid malignancies. Several inflammasome-components were dysregulated in patients with malnutrition, decreased phase angle and dependency grade or increased circulating inflammation markers. A molecular fingerprint based on gene-expression of certain inflammasome factors (p27/CCL2/ASC) in PBMCs accurately differentiated patients with and without malnutrition. In conclusion, malnutrition induces a profound alteration in the gene-expression pattern of inflammasome-machinery components in PBMCs. A comprehensive nutritional assessment including novel morphofunctional techniques and molecular markers allows a broad characterization of the nutritional status in cancer patients. Profile of certain inflammasome-components should be further studied as potential targets for nutrition-focused treatment strategies in cancer patients.

Highlights

Malnutrition may affect 25–50% of patients with head and neck cancers before treatment [1], being severe in about 30% of cases, especially those patients with tumors localized in the oropharynx or the hypopharynx [2]
To the best of our knowledge, this is the first report demonstrating that the expression of specific and relevant inflammasome components is drastically dysregulated in patients with malnutrition and head and neck cancers, and that a comprehensive nutritional and molecular assessment, including novel morphofunctional techniques and molecular markers can be really useful to obtain a broad characterization of the nutritional status in patients with head and neck cancers
Our results reveal novel conceptual and functional pathways in the nutrition field with potential clinical implications, by demonstrating for the first time that a morphofunctional and molecular nutritional assessment in patients with head and neck cancer could be useful to obtain a broad characterization of the nutritional status in these patients

Summary

Introduction

Malnutrition may affect 25–50% of patients with head and neck cancers before treatment [1], being severe in about 30% of cases, especially those patients with tumors localized in the oropharynx or the hypopharynx [2]. Malnutrition is related to a higher rate of postsurgical complications, worse treatment response and higher tumor recurrence as well as increases the risk of infections and treatment related toxicity and decreases quality of life/life expectancy [3]. Malnutrition is related with systemic treatment toxicity and to the tumor itself [1]. Loss of fat-free body mass has been proposed as a direct cause for increased mortality and worse prognosis in cancer patients [6], even in patients whose body mass index (BMI) classifies them as overweight, obese or normal [7]

Objectives

Methods

Results

Discussion

Conclusion