Home›Oncology› ANXA1 dominance independently predicts recurrence in colorectal cancer (HR 1.43)
ANXA1 dominance independently predicts recurrence in colorectal cancer (HR 1.43)New Biomarkers Help Doctors Predict Outcomes for Patients with Colorectal Cancer
medRxivPublished October 31, 2026Study authors: Rotte-Wettig, H. S.; Domingo, E.; Valbuena, G.; Nasreddin, N.; Harkin, A.; Iveson, T.; Saunders, M. …DOI ↗Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development
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Key Takeaway
Interpret ANXA1 dominance as a prognostic biomarker only, not a treatment guide.
This was a translational biomarker analysis of tissue microarrays from patients enrolled in the randomized SCOT trial (n=2163), a colorectal cancer cohort. ANXA1 and LGR5 expression were measured by dual-colour in situ hybridisation and quantified with AI-based digital pathology, alongside image-based consensus molecular subtyping (imCMS).
ANXA1 expression was highest in CMS1 and LGR5 highest in CMS2, with CMS3 and CMS4 intermediate. ANXA1 dominance was associated with right-sided tumors, mismatch repair deficiency, BRAF-V600E mutation, high stromal content, T4 stage, low stromal FoxP3, and high epithelial CD68 density.
For outcomes, combining both markers improved prognostic discrimination compared with either marker alone for cancer-specific survival (p<0.001) and recurrence-free interval (p=0.004). ANXA1 dominance remained an independent predictor of recurrence after adjustment (HR 1.43, 95% CI 1.08-1.90, p=0.014).
Safety and tolerability data were not reported, as this was a biomarker substudy rather than a treatment comparison. Follow-up duration was not reported. The authors describe the findings as associational and prognostic, and do not claim that ANXA1 causes aggressive biology or that these markers have clinical utility or treatment guidance implications.
These results should be interpreted as hypothesis-generating biomarker associations within the SCOT trial cohort and not generalized beyond it. No practice-changing implications are established.
How this fits prior evidence
This biomarker substudy extends prior coverage of molecularly defined colorectal cancer, including BRAF-directed regimens linked to a 22.3-month median OS in BRAF-mutant mCRC. Here, ANXA1 dominance was associated with BRAF-V600E mutation and independently with recurrence (HR 1.43), adding prognostic context to that BRAF-mutant subgroup discussion without addressing treatment selection. It also contrasts with prior treatment-focused coverage such as SCRT-based TNT in locally advanced rectal cancer and thymosin in colorectal cancer with low certainty, since this analysis reports no intervention or safety data. The finding addresses a gap in prognostic biomarker stratification rather than therapeutic efficacy.
Researchers studied a large group of patients with colorectal cancer to see if specific markers in their tissue could help predict the future of the disease. They looked at two specific markers called ANXA1 and LGR5. These markers help doctors understand the different types of cancer and how the body's immune system reacts to the tumor.
The study found that these markers appear in different amounts depending on the type of cancer. For example, one marker was more common in certain types of tumors, while the other was common in different ones. When doctors looked at these markers together, they were able to tell the difference between different cancer types much more clearly than using just one marker alone.
Most importantly, using both markers together helped doctors predict how long a patient might live and how likely the cancer was to return. One specific marker, ANXA1, was linked to a higher risk of the cancer coming back. By looking at these markers together, doctors can get a clearer picture of the disease, which helps in understanding the best way to monitor and manage the cancer for each individual patient.
What this means for you:
Using two markers together helps doctors better predict cancer recurrence and improve survival outlooks.
Common questions
What is ANXA1 and how does it affect colorectal cancer?
ANXA1 is a protein measured in this study. High levels of ANXA1 (called ANXA1 dominance) were linked to a higher risk of cancer recurrence (HR 1.43). It was also associated with certain tumor features like right-sidedness and mismatch repair deficiency. This is an association, not proof that ANXA1 causes cancer to come back.
How does combining ANXA1 and LGR5 improve prognosis?
In the study, looking at both markers together gave a better prediction of cancer-specific survival (p<0.001) and recurrence-free interval (p=0.004) than using either marker alone. This suggests that a combined marker approach could help doctors better understand a patient's outlook, but more research is needed before it's used in practice.
Who does this research apply to?
The study included 2,163 patients with colorectal cancer who were part of the SCOT trial. The results are based on this specific group, so they may not apply to all people with colorectal cancer. Always talk to your doctor about what these findings mean for your individual situation.
Are there any side effects or safety concerns with these markers?
This study looked at markers in tissue samples, not a treatment, so there were no side effects reported. The research focused on how well the markers predict outcomes, not on safety. If you have questions about your own care, please consult your healthcare provider.
Background: LGR5 and ANXA1 are markers for specific intestinal stem cell states. LGR5+/ANXA1- crypt base columnar cells (CBCs) maintain homeostasis, whereas ANXA1+/LGR5- regenerative stem cells (RSCs) are present in fetal and repairing epithelium. Both states have been described in colorectal cancer (CRC), yet their clinical significance remains unclear. We aimed to determine how ANXA1 and LGR5 expression relates to molecular subtype, immune microenvironment and outcome in CRC. Methods: Dual-colour in situ hybridisation for ANXA1 and LGR5 was performed on tissue microarrays from 2163 patients in the randomised SCOT trial (ISRCTN59757862). AI-based digital pathology quantified marker-positive area by compartment and image based consensus molecular subtype (imCMS). Markers were related to clinicopathological, molecular and immune data, and to survival using Kaplan-Meier and multivariable Cox analyses. Results: ANXA1 and LGR5 showed inverse enrichment among a diverse group of parameters. ANXA1 was highest in CMS1 and LGR5 in CMS2, with CMS3 and CMS4 being intermediate. ANXA1 dominance was associated with right-sidedness, mismatch repair deficiency, BRAF-V600E mutation, high stromal content, T4 stage, low stromal FoxP3 and high epithelial CD68 density. Combining both markers improved prognostic discrimination compared with either alone (cancer-specific survival p<0.001; recurrence-free interval p=0.004), with ANXA1 dominance remaining an independent predictor of recurrence after adjustment (HR 1.43, 95% CI 1.08-1.90, p=0.014). Conclusion: Relative ANXA1 enrichment defines an aggressive, stroma-rich, macrophage-enriched CRC subgroup with poor prognosis.
