Investigation of Microbial Translocation, TLR and VDR Gene Polymorphisms, and Recurrence Risk in Stage III Colorectal Cancer Patients

Abstract

Gut microbial dysbiosis and microbial passage into the peripheral blood leads to colorectal cancer (CRC) and disease progression. Toll-like (TLR) and vitamin D (VDR) receptors play important role in the immune modulation and polymorphisms that may increase CRC risk and death rates. The aim of the current study was to demonstrate the prognostic value of microbial DNA fragments in the blood of stage III CRC patients and correlate such microbial detection to TLR/VDR polymorphisms. Peripheral blood was collected from 132 patients for the detection of microbial DNA fragments, and TLR/VDR gene polymorphisms. In the detection of various microbial DNA fragments, TLR and VDR polymorphisms was significantly higher compared to healthy group. Homozygous individuals of either TLR or VDR polymorphisms had significantly higher detection rates of microbial DNA fragments. Mutational and MSI status were significantly correlated with TLR9 and VDR polymorphisms. Significantly shorter disease-free survival was associated with patients with BRAF mutated tumors and ApaI polymorphisms, whereas shorter overall survival was associated with the detection of C. albicans. The detection of B. fragilis, as demonstrated by the multivariate analysis, is an independent poor prognostic factor for shorter disease-free survival. TLR/VDR genetic variants were significantly correlated with the detection of microbial fragments in the blood, and this in turn is significantly associated with tumorigenesis and disease progression.

Plasma Bacterial DNA Load as a Potential Biomarker for the Early Detection of Colorectal Cancer: A Case–Control Study

“…In particular, recent studies have honed in on its potential role in CRC, a common malignancy with complex etiology. Meta-analyses conducted in recent years have highlighted a significant difference in the diversity of microbial taxa found in the bloodstream, stool and biopsy samples of colon cancer patients compared to healthy individuals [ 14 , 27 , 28 ]. This study focuses on quantifying the levels of circulating bacterial DNA in individuals with CRC.…”

Single Nucleotide Polymorphisms in the Vitamin D Metabolic Pathway as Survival Biomarkers in Colorectal Cancer

“…These polymorphisms could give rise to a modified receptor, affecting its interaction with vitamin D [ 37 ]. Both vitamin D metabolism and the actions of the VDR would therefore be reduced, which could favor tumor progression [ 37 , 38 , 39 ].…”

Microbial sensing in the intestine

“…Epithelial metabolite receptors, such as GPR120, VDR and AHR, are essential for maintaining the mucosal barrier integrity, restoring the gut barrier homeostasis, and preventing CRC development ( Metidji et al, 2018 ; Rubbino et al, 2022 ; Zhang et al, 2022 ). Several VDR gene polymorphisms are significantly associated with colorectal cancer development and progression ( Latacz et al, 2021 ; Messaritakis et al, 2022 ).…”