Abstract
We aim to estimate the diagnostic performances of anterior gradient homolog-2 (AGR2) and Leucine-rich repeat-containing-G-protein-coupled receptor 5 (LGR5) in peripheral blood (PB) as mRNA biomarkers in colorectal cancer (CRC) and to explore their prognostic significance. Real-time PCR was used to analyze AGR2 and LGR5 in 54 stages I-IV CRC patients and 19 controls. Both mRNAs were significantly increased in PB from CRC patients compared to controls. The area under the receiver-operating characteristic curves were 0.722 (p = 0.006), 0.376 (p = 0.123) and 0.767 (p = 0.001) for AGR2, LGR5 and combined AGR2/LGR5, respectively. The AGR2/LGR5 assay resulted in 67.4% sensitivity and 94.7% specificity. AGR2 correlated with pT3–pT4 and high-grade tumors. LGR5 correlated with metastasis, R2 resections and high-grade. The progression-free survival (PFS) of patients with high AGR2 was reduced (p = 0.037; HR, 2.32), also in the stage I-III subgroup (p = 0.046). LGR5 indicated a poor prognosis regarding both PFS (p = 0.007; HR, 1.013) and overall survival (p = 0.045; HR, 1.01). High AGR2/LGR5 was associated with poor PFS (p = 0.014; HR, 2.8) by multivariate analysis. Our findings indicate that the assessment of AGR2 and LGR5 in PB might reflect the presence of circulating tumor cells (CTC) and stem cell like CTC in CRC. Increased AGR2 and LGR5 are associated with poor outcomes.
Highlights
Colorectal cancer (CRC) is one of the leading causes of cancer-associated morbidity and mortality across the world
Our findings revealed that molecular assessment of anterior gradient homolog-2 (AGR2) and Leucine-rich repeat-containing-G-protein-coupled receptor 5 (LGR5) can serve as a marker of circulating tumor cells (CTC) and intestinal stem-cell (ISC)-like CTC in colorectal cancer (CRC) patients, which underscores their potential clinical relevance as predictors of disease outcome
Our findings indicate a high sensitivity and specificity for AGR2/LGR5 quantitative real-time reverse-transcription PCR (qRT-PCR) for the surrogate detection of CTC in peripheral blood (PB) samples and it could be useful as a prognostic factor in patients with CRC
Summary
Colorectal cancer (CRC) is one of the leading causes of cancer-associated morbidity and mortality across the world. Sensitive methods to detect circulating tumor cells (CTC) could serve as prognostic or predictive tools to identify patients at a high risk of disease progression who could be selected for additional treatment [2]. [20,21] it was shown that the LGR5 gene and protein were markedly over expressed in the majority of advanced CRCs and in CRC cell lines derived from metastatic tumors. We hypothesized that LGR5 mRNA expression in PB of CRC patients could indicate the presence of circulating tumor cells with stem cell properties. The blood expression of the intestinal stem-cell (ISC) marker LGR5 was evaluated for correlations with AGR2 and clinical parameters. Our findings revealed that molecular assessment of AGR2 and LGR5 can serve as a marker of CTC and ISC-like CTC in CRC patients, which underscores their potential clinical relevance as predictors of disease outcome
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
