Circulating PTGS2, JAG1, GUCY2C and PGF mRNA in Peripheral Blood and Serum as Potential Biomarkers for Patients with Metastatic Colon Cancer

Abstract

Genes involved in the angiogenic process have been proposed for the diagnosis and therapeutic response of metastatic colorectal cancer (CRC). This study aimed to investigate the value of PTGS2, JAG1, GUCY2C and PGF-circulating RNA as biomarkers in metastatic CRC. Blood cells and serum mRNA from 59 patients with metastatic CRC and 47 healthy controls were analyzed by digital PCR. The area under the receiver operating characteristic curve (AUC) was used to estimate the diagnostic value of each mRNA alone or mRNA combinations. A significant upregulation of the JAG1, PTGS2 and GUCY2C genes in blood cells and serum samples from metastatic CRC patients was detected. Circulating mRNA levels in the serum of all genes were significantly more abundant than in blood. The highest discrimination ability between metastatic CRC patients and healthy donors was obtained with PTGS2 (AUC of 0.984) and GUCY2C (AUC of 0.896) in serum samples. Biomarker combinations did not improve the discriminatory capacity of biomarkers separately. Analyzed biomarkers showed no correlation with overall survival or progression-free survival, but GUCY2C and GUCY2C/PTGS2 expression in serum correlated significantly with the response to antiangiogenic agents. These findings demonstrate that assessment of genes involved in the angiogenic process may be a potential non-invasive diagnostic tool for metastatic CRC and its response to antiangiogenic therapy.

Extracellular Nucleic Acids in the Diagnosis and Progression of Colorectal Cancer

“…A study by Pun et al [ 110 ] has revealed that plasma levels of the Bmi1 transcript may be used as a biomarker in mCRC patients for non-invasive monitoring of occult metastases and anticipating the emergence of distant metastases. mRNA produced from the genes prostaglandin-endoperoxide synthase 2 ( PTGS2 ), guanylate cyclase 2C ( GUCY2C ) and jagged canonical notch ligand 1 ( JAG1 ) were reported to be upregulated in mCRC, while the serum expression of GUCY2C and GUCY2C/PTGS2 showed correlation with the therapeutic response [ 111 ]. However, a definitive prognostic cf-mRNA biomarker for response to therapy and survival of mCRC patients has yet to emerge.…”

Facile Synthesis of Bifunctional Metal–Organic Framework Nanoparticles for Isolation of Extracellular Vesicles

“…As was mentioned above, the SW620-EVs significantly promoted the migration of HUVECs; therefore, we conducted RT-PCR for tumor-related mRNA screening of SW480-EVs and SW620-EVs and also detected EVs isolated from cell medium of human primary CRC cells HCT116 (HCT116-EVs) to achieve a more accurate differential expression analysis. As shown in Figure 5a, some upregulated mRNAs in the SW620-EVs have been reported to be involved in CRC angiogenesis, including ADM, 34,35 BPTF, 36 FZD5, 37,38 ID1, 39 JAG1, 40,41 PGF, 42 and PIK3C2A. 43,44 In addition, FAM83D, 45 LPR1, 46 and YWHAZ, 47 which were more highly expressed in SW620-EVs than in SW480-EVs and HCT116-EVs, were also closely related to tumor development (Figure S7).…”

ASCA-related antibodies in the blood sera of healthy donors and patients with colorectal cancer: characterization with oligosaccharides related to Saccharomyces cerevisiae mannan

“…Of note, this ligand was recently introduced as a new high-affinity ligand for DC-SIGN, a basic receptor of the innate immune system ( Krylov et al, 2023 ). Due to the low sensitivity and specificity of existing screening methods, much effort is focused on finding new potential biomarkers for colon cancer ( Jimenez-Luna et al, 2021 ). Tumor and normal tissues are characterized by different glycosylation profiles ( Zhao et al, 2018 ); in particular, high-mannose N-glycans are regarded as markers of malignant progression in the early stages of colorectal cancer ( Boyaval et al, 2022 ).…”