LGR5 rs17109924 is a predictive genetic biomarker for time to recurrence in patients with colon cancer treated with 5-fluorouracil-based adjuvant chemotherapy

Abstract

We recently found variants in cancer stem cell genes (CD44, ALCAM and LGR5) significantly associated with increased time to recurrence (TTR) in patients with stage III and high-risk stage II colon cancer treated with 5-fluorouracil (5-FU)-based chemotherapy. In this study, we validated these genetic biomarkers in a large and independent patient cohort (n=599). Patients who received 5-FU-based adjuvant chemotherapy (n=391) carrying at least one C allele in LGR5 rs17109924 had a significantly increased TTR compared with patients carrying the homozygous T/T variant (HR 0.38, 95%CI 0.19–0.79; P=0.006). In patients treated with surgery alone (n=208), no association between LGR rs17109924 and TTR was found (P=0.728). In the multivariate Cox-analysis, LGR5 rs17109924 remained statistically significant (HR 0.38, 95%CI 0.18–0.78; P=0.008) for patients who received adjuvant chemotherapy. We confirmed in a large and independent study cohort that LGR5 rs17109924 is a predictive genetic biomarker for TTR in patients with colon cancer treated with 5-FU-based adjuvant chemotherapy.

Dickkopf-2 regulates the stem cell marker LGR5 in colorectal cancer via HNF4α1

“…Increased expression of the intestinal stem cell marker gene LGR5 is commonly observed in colorectal cancers ( Leushacke and Barker, 2012 ; Szkandera et al., 2015 ; Li et al., 2016 ). Recent studies have shown that depletion of LGR5 expressing cells suppressed metastatic progression of colon cancer in murine model systems ( de Sousa e Melo et al., 2017 ; Fumagalli et al., 2020 ).…”

Targeting LGR5 in Colorectal Cancer: therapeutic gold or too plastic?

“… 44 In contrast, an allelic variant of the same SNP (rs17109924) predicts better response to 5FU-based adjuvant chemotherapy. 45 However, neither study demonstrated how the SNP impacted LGR5 expression, which is crucial given that primary colorectal carcinomas harbouring variant LGR5 genotypes can exhibit significantly lower LGR5 protein expression. 37…”

LGR5, HES1 and ATOH1 in Young Rectal Cancer Patients in Egyptian

“…Most of the studies primarily depend on IHC, which is highly altered by methodological factors. Another potential mechanism to the opposing results is variants of the LGR5 gene (Kleist et al, 2012;Szkandera et al, 2015).…”