An Increased Level of Aryl Hydrocarbon Receptor in Patients with Pancreatic Cancer

Abstract

BACKGROUND Aryl-carbon receptor (AhR), a ligand-activated transcription factor, is best known for its ability to mediate the effects of environmental toxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. AhR is expressed in several tumor cells and regulates the expression of genes in the signal transduction pathways. In this study, we examined the soluble levels of AhR in patients with pancreatic cancer. METHODS 123 samples, including 59 (48%) samples of pancreatic ductal adenocarcinoma based on histological evidence and 64 (52%) healthy control samples, were evaluated to determine plasma levels of AhR by Enzyme-linked immunoassay. RESULTS The median of AhR among patients was 0.280 ng/mL, which differed considerably from 0.07 ng/mL in the control group (p < 0.001). Significant differences of the AhR were observed between the plasma samples of the patients compared with the healthy group, with respect to male sex (p < 0.001), age groups (p = 0.001), diabetic status (p < 0.001), body mass index (BMI) categories (p = 0.035), and constantly smokers (p < 0.001). We also observed significant differences between the level of AhR expression between men and women (p = 0.01) and ever to never smokers (p = 0.009) in the case group. In addition, the age of 65 and a BMI of 25 or less were significant factors in plasma AhR levels ([1.61 95%CI 1.08-2.38] and [1.84 95%CI 1.22-2.77], respectively). CONCLUSION The results of this study can add diagnostic information to pancreatic cancer involving AhR and the potential efficacy of this receptor in therapeutic strategies.

AhR and Cancer: from Gene Profiling to Targeted Therapy

“…Indeed, AhR mRNA is overexpressed in breast cancer [12] [13], lung cancer [14], thyroid cancer [15], and oral squamous cell carcinoma (OSCC) [16]. A high level of AhR protein has also been reported in pancreatic cancer [17], endometrial cancer [18], and meningioma [19]. Such elevated AhR expression appears to correlate with the stage of tumor progression independently of the tumor type (Fig.…”

Dehydroepiandrosterone modulates oxidative DNA damage in pancreatic cancer: A case–control study

“…Changes in redox metabolism in the metabolic reprogramming of nearly all cancers were associated with the accumulation of reactive oxygen species (ROS) 6 . ROS are free radicals that are an extremely dynamic material for cell damage and are produced during the transport of electrons from the mitochondria of living cells 7,8 . At high concentrations, ROS induce oxidative damage, especially in DNA, then causing mutations that ultimately lead to cancer 6…”

AhR and Cancer: From Gene Profiling to Targeted Therapy

“…Indeed, AhR mRNA is overexpressed in breast cancer [ 12 , 13 ], lung cancer [ 14 ], thyroid cancer [ 15 ], and oral squamous cell carcinoma (OSCC) [ 16 ]. A high level of AhR protein has also been reported in pancreatic cancer [ 17 ], endometrial cancer [ 18 ], and meningioma [ 19 ]. Median expression of AhR appears elevated from stage I, independently of the tumor type, suggesting that this increased expression is an early event in many cancer ( Figure 1 C).…”