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Comprehensive Characterization of Tumor Genetic, Metabolic, and Inflammatory Profiles in Colorectal Cancer Patients: Insights from Adipose Tissue Analysis

Abstract

Cancer cachexia is a common condition among patients with rectal cancer. It is characterized by involuntary and severe weight loss, accompanied by changes in body composition, such as the loss of lean mass and alterations in adipose tissue. Interestingly, there is significant heterogeneity in the prevalence and extent of cachexia among patients with the same type of tumor. This variation is believed to be associated with both tumor and individual characteristics, both genotypic and phenotypic. The GDF15 protein has recently gained attention in the context of cachexia as it influences food intake, energy homeostasis, and body weight control. However, there is still a challenge in understanding how these changes precisely impact the pathophysiology of cachexia. Our research group has been dedicated to investigating the impact of changes in body composition on the survival of patients with various types of cancer. In a recent observation, we found that higher radiodensity of adipose tissue is linked to increased glucose uptake from this tissue and higher levels of serum inflammatory cytokines. Additionally, it is associated with worse survival in patients with multiple myeloma. Intriguingly, the high radiodensity of subcutaneous adipose tissue shows a Hounsfield Unit (HU) value similar to brown adipose tissue, suggesting that it might be an early marker of cachexia, indicating the conversion of white adipose tissue to "beige" adipose tissue. Nevertheless, high radiodensity values may also indicate greater inflammation of adipose tissue, increased infiltration of activated macrophages, and consequently, higher glucose uptake. In this study, we aimed to investigate the genomic profile of the tumor using nanostring analysis, as well as examine body composition and radiodensity of muscle and adipose tissue through computed tomography. Additionally, we will measure glucose uptake from subcutaneous and visceral adipose tissue using Positron Emission Tomography/Computed Tomography with 18F-fluorodeoxyglucose (FDG-PET/CT). Furthermore, we will analyze the profile of adipose tissue through single-cell RNA sequencing, and measured the serum concentration of GDF15, along with metabolic and inflammatory markers in serum and tumor and adipose tissue samples. These investigations were conducted on patients with rectal cancer who were being treated at the oncology outpatient clinic of the Hospital de Clínicas of the State University of Campinas. By conducting this comprehensive study, we aim to enhance our understanding of the changes occurring in the adipose tissue of cancer patients. Ultimately, we hope to develop a clinical tool that can detect cachexia at an early stage, thus facilitating timely intervention and management of this condition. (AU)

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