# Prognostic and predictive value of AXL and C-MET in patients with rectal cancer

**Authors:** Carmen Austrália Paredes Marcondes RIBAS, Efstathia N DOELKEN, Sudipta TRIPATHI, Bülent POLAT, Reinhard LISSNER, Thomas BÖELDICKE, Jurandir Marcondes RIBAS-FILHO, Osvaldo MALAFAIA, Martin GASSER, Ana Maria WAAGA-GASSER

PMC · DOI: 10.1590/0102-67202025000049e1918 · 2026-01-19

## TL;DR

This study investigates the potential of AXL and C-MET as biomarkers in rectal cancer, finding that C-MET may predict treatment response, while AXL levels differ from healthy individuals but lack prognostic value.

## Contribution

The study evaluates AXL and C-MET as novel biomarkers for rectal cancer prognosis and treatment response prediction.

## Key findings

- AXL serum levels were significantly different in rectal cancer patients compared to healthy subjects.
- C-MET levels in serum increased after neoadjuvant therapy and may predict treatment response.
- Tumor tissue showed stage-dependent increases in marker expression, but serum markers did not correlate with survival.

## Abstract

Rectal cancer remains a significant clinical challenge with demand for conclusive biomarkers, essential in prognostication and therapy monitoring of neoadjuvant and adjuvant treatment strategies.

The aim of the study was to evaluate AXL and cellular mesenchymal-epithelial transition factor (C-MET) biomarkers for cancer stem cells and to correlate them with clinicopathological characteristics and patient outcome data with respect to neoadjuvant chemoradiotherapy.

Serum levels of soluble surface markers AXL and C-MET were retrospectively analyzed in 164 rectal cancer patients with additional immunofluorescent analyses of their primary tumor tissues.

Kaplan-Meier analysis confirmed the prognostic significance of Union for International Cancer Control stages, but with no significant correlation between investigated markers with patient age, gender, or tumor stage. In contrast, tumor tissues demonstrated stage-dependently increased marker expression. While AXL was detected at low levels, C-MET exhibited a bimodal distribution, with elevated levels seen in most patients, particularly post-neoadjuvant therapy and non-significantly in the subgroup with poorer response to neoadjuvant therapy (p=0.074).

AXL serum levels in the rectal cancer cohort were significantly different from healthy subjects but did not correlate with tumor stage or survival during and after neoadjuvant/adjuvant therapy. Soluble C-MET levels in the blood, influenced by neoadjuvant chemoradiotherapy, may serve as a predictive marker for treatment response.

Rectal carcinoma remains a significant global health challenge due to the risk of developing the disease increasing steadily with advancing age.

Preoperative assessment of serum tumor markers provides valuable prognostic and therapeutic information in solid tumors.

Persistently elevated tumor markers, despite resection, suggest residual disease or not detectable micrometastases, which may guide decisions on adjuvant therapy.

Rectal cancer patients showed elevated C-MET levels in their serum, which were correlated with its expression in the respective patient tumors. Serum levels for AXL were found to be diminished.

Neoadjuvant chemoradiotherapy resulted in elevated C-MET levels, suggesting that it may serve as a predictive marker for treatment response.

Rectal cancer remains a significant clinical challenge, with demand for conclusive biomarkers essential in prognostication and therapy monitoring of neoadjuvant and adjuvant treatment strategies. Serum levels of soluble surface markers AXL and C-MET, described for cancer stem cells in rectal cancer, possibly can correlate with clinicopathological characteristics and patient outcome data with respect to neoadjuvant chemoradiotherapy.

AXL and C-MET serum levels in rectal cancer are significantly different from healthy subjects but did not correlate with tumor stage or survival during and after neoadjuvant/adjuvant therapy, while C-MET may hold promise for influencing future treatment responses.

## Linked entities

- **Genes:** AXL (AXL receptor tyrosine kinase) [NCBI Gene 558], MET (MET proto-oncogene, receptor tyrosine kinase) [NCBI Gene 4233]
- **Diseases:** rectal cancer (MONDO:0006519)

## Full-text entities

- **Genes:** AXL (AXL receptor tyrosine kinase) [NCBI Gene 558] {aka ARK, AXL3, JTK11, Tyro7, UFO}
- **Diseases:** Cancer (MESH:D009369), Rectal cancer (MESH:D012004)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12815463/full.md

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Source: https://tomesphere.com/paper/PMC12815463