Body Composition, Inflammation, and 5-Year Outcomes in Colon Cancer

Abstract

IMPORTANCE Obesity, particularly visceral obesity and sarcopenia, are poor prognostic indicators in colon cancer. OBJECTIVES To explore the association between body composition profiles and 5-year colon cancer outcomes and delineate the associated underlying inflammatory processes. DESIGN, SETTING, AND PARTICIPANTS This multicenter translational cohort study included patients with nonmetastatic colon cancer who did not have underlying chronic inflammatory disorders and were not receiving anti-inflammatory drugs referred to tertiary cancer centers from 2009 to 2015. Preoperative acute phase proteins (white cell count, C-reactive protein, and albumin), cytokines (interleukin [IL]-1b, IL-2, IL-6, IL-10, interferon γ, and tumor necrosis factor α), vascular endothelial growth factor (VEGF), and cell surface receptor expression levels (CD11b and CD14) were measured. All patients underwent follow-up for at least 5 years. Data were analyzed in December 2020. EXPOSURE Nonmetastatic colon cancer. MAIN OUTCOMES AND MEASURES The associations of body composition profiles with 5-year cancer recurrence and disease-specific mortality were analyzed using Mantel Cox log-rank test and Kaplan-Meier curves. RESULTS A total of 28 patients were included (median [interquartile range] age, 67 [58-72] years;22 [78.6%] men). Low skeletal muscle area (SMA) and high visceral to total fat ratio were associated with poor clinical and oncological outcomes, including increased 5-year recurrence (low SMA: hazard ratio [HR], 2.30 [95% CI, 1.41-2.89]; P = .04; high visceral to total fat ratio: HR, 5.78 [95% CI, 3.66-7.95]; P = .02). High visceral to total fat ratio was associated with increased 5-year disease-specific mortality (HR,5.

Acute or chronic inflammation role in gastrointestinal oncology

“…On the other hand, external stimuli, such as excessive oxidative stress, promote the secretion and release of the IL family, while the IL family itself has a certain feedback activation effect, thus exacerbating the inflammatory response[ 5 ]. In colitis-cancer, IL-6 and other factors promote epidermal cell damage, and prolonged inflammatory damage will lead to abnormal proliferation of epidermal cells, which if not controlled will eventually lead to gene epigenetic modification mutation and ultimately induce tumorigenesis[ 6 , 7 ].…”

“…The new clinical research paper indicated that colon cancer patients with higher IL-6 and TNF (chronic inflammatory factors) developed a cancer recurrence. However, acute inflammatory factors, IL-10 and interferon γ, were lower in expression compared with those who did not recur[ 7 ]. IL-12 is an acute inflammatory factor that could inhibit tumor progression in gastrointestinal tumors, and its high expression leads to a longer survival time[ 12 ].…”

Visceral Obesity: Terminology, Measurement, and Its Correlation with Inflammation

“…Данное депо не обладает большой емкостью, что приводит к гипертрофии адипоцитов ВЖТ, их гибели и, как следствие, дифференцировке мигрировавших в ВЖТ моноцитов в макрофаги М1 [40,41]. Результаты ряда работ подтверждают участие этих клеток в развитии воспаления посредством синтезируемых ими цитокинов -интерлейкинов (IL) 6, 1␤, фактора некроза опухоли альфа (TNF-␣), моноцитарного хемотаксического белка (МCP-1) и рецептора ␤ хемокинов (CCR2), молекул клеточной адгезии ICAM, VCAM, P-и E-селектинов [42][43][44]. В исследовании R. Mujkiс и соавт., проведенном с участием мальчиков в возрасте от 2 до 16 лет с избыточной жировой тканью и ожирением, показано, что количество макрофагов было выше в ВЖТ, нежели в подкожной жировой клетчатке [45].…”

“…Цитокины IL-6 и TNF-␣, синтезируемые макрофагами, играют важную роль в развитии инсулинорезистентности [40,42]. Способствуя высвобождению из адипоцитов свободных жирных кислот, они также опосредуют синтез цитокинов, хемокинов, церамидов, сфингозин-1-фосфата (S1P), что влечет за собой нарушение передачи сигналов инсулина к клеткам [41,46,47].…”

Dermatopontin Influences the Development of Obesity-Associated Colon Cancer by Changes in the Expression of Extracellular Matrix Proteins

“…Different risk factors associated with the development and prognosis of CC are preventable, comprising an excessive intake of red and processed meat, consumption of high-fat diets, a low intake of vegetables and fruits, physical inactivity, alcohol drinking, smoking and obesity [ 2 , 3 , 4 ]. Epidemiological studies evidenced a significant impact of obesity not only on the risk of developing gastrointestinal cancer but also on its diagnosis and treatment [ 5 ]. Specifically, dysfunctional adipose tissue (AT) in obesity has been closely associated with tumour growth and metastasis, with chronic and unresolved inflammation together with the altered extracellular matrix (ECM) remodelling and fibrosis constituting key factors in this association [ 6 , 7 ].…”