Obesity is a risk factor for intrahepatic cholangiocarcinoma progression associated with alterations of metabolic activity and immune status

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.

Feedback Signaling between Cholangiopathies, Ductular Reaction, and Non-Alcoholic Fatty Liver Disease

“…understood that NAFLD is a risk factor for the development of hepatocellular carcinoma, but one study found that NAFLD may increase the risk of CCA development [63]. This work is supported by other findings indicating that obesity may promote CCA progression, as indicated by larger tumor size and increased metastasis in obese CCA patients compared with normal weight counterparts [64]. Others have found that NASH, but not NAFLD, was a significant risk factor for CCA development and worse prognosis [65].…”

Impact of JMJD6 on intrahepatic cholangiocarcinoma

“…Therefore, we performed RNA sequencing to elucidate the genes regulated by JMJD6, which resulted in the identification of 171 candidate genes. Our institution has previously reported the impact of tumor immunology on cancer prognosis ( 12 , 25 , 26 ); thus, we focused on immune-related genes. We found that PD-L1 mRNA levels increased in response to JMJD6 knockdown, indicating that JMJD6 regulates PD-L1 expression.…”

A Predictive Model Based on the Gut Microbiota Improves the Diagnostic Effect in Patients With Cholangiocarcinoma

“…In addition, genus Ruminococcaceae can help reduce polysaccharide degradation and reverses dextran sodium sulfate to preserve intestinal barrier integrity ( Wang et al., 2019 ). Previous studies suggested that gut microbiota was associated with body weight ( Cuevas-Sierra et al., 2019 ), and obesity might be a risk factor for CCA progression and postoperative recurrence ( Merath et al., 2019 ; Zhou et al., 2020 ; Yugawa et al., 2021 ). There was evidence concerning the potential role of gut microbiota and probiotic-derived extracellular vesicles (EVs) on obesity via the modulation of inflammation, metabolism, and gut permeability ( Díez-Sainz et al., 2021 ).…”