Abstract
Body mass index (BMI) is well known to be associated with poor prognosis in several cancers. The relationship between BMI and the long-term outcomes of patients with intrahepatic cholangiocarcinoma (ICC) is incompletely understood. This study investigated the relationships of BMI with clinicopathological characteristics and patient outcomes, focusing on metabolic activity and immune status. The relationship between BMI and the maximum standardized uptake value (SUVmax) on fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) was analyzed. In addition, immunohistochemistry was performed for programmed cell death-ligand 1 (PD-L1), cluster of differentiation 8 (CD8), and forkhead box protein P3 (Foxp3). Seventy-four patients with ICC were classified into normal weight (BMI < 25.0 kg/m2, n = 48) and obesity groups (BMI ≥ 25.0 kg/m2, n = 26), respectively. Serum carbohydrate antigen 19–9 levels were higher in the obesity group than in the normal weight group. Tumor size and the intrahepatic metastasis rate were significantly larger in the obesity group. Patients in the obesity group had significantly worse prognoses than those in the normal weight group. Moreover, BMI displayed a positive correlation with SUVmax on 18F-FDG PET/CT (n = 46, r = 0.5152). Patients with high 18F-FDG uptake had a significantly higher rate of PD-L1 expression, lower CD8 + tumor-infiltrating lymphocyte (TIL) counts, and higher Foxp3 + TIL counts. The elevated BMI might predict the outcomes of patients with ICC. Obesity might be associated with ICC progression, possibly through alterations in metabolic activity and the immune status.
Highlights
Body mass index (BMI) is well known to be associated with poor prognosis in several cancers
glucose transporter 1 (GLUT1) Glucose transporter 1 hepatocellular carcinoma (HCC) Hepatocellular carcinoma hypoxia-inducible factor 1A (HIF-1A) Hypoxia-inducible factor 1A intrahepatic cholangiocarcinoma (ICC) Intrahepatic cholangiocarcinoma Immune checkpoint inhibitors (ICIs) Immune checkpoint inhibitor NAFLD Non-alcoholic fatty liver disease NAS NAFLD activity score non-alcoholic steatohepatitis (NASH) Non-alcoholic steatohepatitis overall survival (OS) Overall survival positron emission tomography/computed tomography (PET/CT) Positron emission tomography/computed tomography programmed cell death-ligand 1 (PD-L1) Programmed death-ligand 1 recurrence-free survival (RFS) Recurrence-free survival receiver operating characteristic (ROC) Receiver operating characteristic SUVmax Maximum standardized uptake value tumor-infiltrating lymphocyte (TIL) Tumor-infiltrating lymphocytes tumor microenvironment (TME) Tumor microenvironment
We found that increased BMI among patients undergoing curative resection for ICC was significantly associated with poor prognosis and an increased risk of recurrence
Summary
Body mass index (BMI) is well known to be associated with poor prognosis in several cancers. The relationship between BMI and the maximum standardized uptake value (SUVmax) on fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) was analyzed. Abbreviations BMI Body mass index CA19-9 Carbohydrate antigen 19-9 CD8 Cluster of differentiation 8 CEA Carcinoembryonic antigen CI Confidence interval CT Computed tomography 18F-FDG Fluorine-18 fluorodeoxyglucose Foxp[3] Forkhead box protein P3. GLUT1 Glucose transporter 1 HCC Hepatocellular carcinoma HIF-1A Hypoxia-inducible factor 1A ICC Intrahepatic cholangiocarcinoma ICI Immune checkpoint inhibitor NAFLD Non-alcoholic fatty liver disease NAS NAFLD activity score NASH Non-alcoholic steatohepatitis OS Overall survival PET/CT Positron emission tomography/computed tomography PD-L1 Programmed death-ligand 1 RFS Recurrence-free survival ROC Receiver operating characteristic SUVmax Maximum standardized uptake value TILs Tumor-infiltrating lymphocytes TME Tumor microenvironment. We hypothesize that the metabolic disorders caused by obesity are associated with tumor progression via alterations of the immune status
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