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Purpose <p>Colorectal cancer (CRC) treatment failure results in high mortality. The current CRC treatment response monitoring blood biomarker carcinoembryonic antigen (CEA) lacks specificity. Methylated <i>BCAT1/IKZF1</i> circulating tumour DNA (ctDNA) indicates CRC, but its utility during therapy is uncertain. This study examined whether during-treatment measurement of <i>BCAT1/IKZF1</i> ctDNA reflects CRC treatment efficacy.</p> Methods <p>Plasma was collected from CRC patients before and during chemotherapy, targeted therapy and/or radiotherapy. Cell-free DNA was extracted, bisulphite-converted and assayed via multiplex qPCR for <i>BCAT1/IKZF1</i> methylation (%pg/<i>ACTB</i>). Patients with detectable ctDNA pre-treatment were included. CEA was measured via chemiluminescent immunoassay. Radiological treatment response assessments were performed ± 3&#xa0;months of blood collection or &lt; 8&#xa0;months post-treatment. Biomarker levels were compared using Mann–Whitney U and Kruskal–Wallis tests.</p> Results <p>56 samples from 29 patients (64.3% male, median age 55&#xa0;years) were analysed. Patients with residual cancer had higher ctDNA levels (median 0.036%, IQR 0–1.17%) than cancer-free patients (0%, IQR 0–0.005%; <i>p</i> &lt; 0.05). There were no significant differences for CEA. When normalised to pre-treatment measurements, treatment-responders demonstrated a median 100% ctDNA reduction from baseline (IQR − 100% to − 7.53%), which was greater than non-responders (0.13% reduction, IQR − 38.1% to + 0.03%; <i>p</i> &lt; 0.001). Responders also demonstrated greater CEA reduction (median − 1.50&#xa0;ng/mL, IQR − 6.28 to 0.18&#xa0;ng/mL) compared to non-responders (median 2.3&#xa0;ng/mL, IQR − 0.50 to 17.7&#xa0;ng/mL; <i>p</i> = 0.001).</p> Conclusions <p>Methylated <i>BCAT1</i>/<i>IKZF1</i> ctDNA reflects treatment response, offering a tool for personalised treatment.</p>

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Investigation of a methylated BCAT1 and IKZF1 circulating tumour DNA blood test for monitoring treatment response in patients with colorectal cancer

  • 期刊论文

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  • 发表日期：

    2026年6月2日

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  • Rafha Rafeeu,
  • Erin L. Symonds,
  • Michael Z. Michael,
  • Kathryn Cornthwaite,
  • Susanne K. Pedersen,
  • Renee J. Smith,
  • Graeme P. Young,
  • Jean M. Winter

摘要

Purpose

Colorectal cancer (CRC) treatment failure results in high mortality. The current CRC treatment response monitoring blood biomarker carcinoembryonic antigen (CEA) lacks specificity. Methylated BCAT1/IKZF1 circulating tumour DNA (ctDNA) indicates CRC, but its utility during therapy is uncertain. This study examined whether during-treatment measurement of BCAT1/IKZF1 ctDNA reflects CRC treatment efficacy.

Methods

Plasma was collected from CRC patients before and during chemotherapy, targeted therapy and/or radiotherapy. Cell-free DNA was extracted, bisulphite-converted and assayed via multiplex qPCR for BCAT1/IKZF1 methylation (%pg/ACTB). Patients with detectable ctDNA pre-treatment were included. CEA was measured via chemiluminescent immunoassay. Radiological treatment response assessments were performed ± 3 months of blood collection or < 8 months post-treatment. Biomarker levels were compared using Mann–Whitney U and Kruskal–Wallis tests.

Results

56 samples from 29 patients (64.3% male, median age 55 years) were analysed. Patients with residual cancer had higher ctDNA levels (median 0.036%, IQR 0–1.17%) than cancer-free patients (0%, IQR 0–0.005%; p < 0.05). There were no significant differences for CEA. When normalised to pre-treatment measurements, treatment-responders demonstrated a median 100% ctDNA reduction from baseline (IQR − 100% to − 7.53%), which was greater than non-responders (0.13% reduction, IQR − 38.1% to + 0.03%; p < 0.001). Responders also demonstrated greater CEA reduction (median − 1.50 ng/mL, IQR − 6.28 to 0.18 ng/mL) compared to non-responders (median 2.3 ng/mL, IQR − 0.50 to 17.7 ng/mL; p = 0.001).

Conclusions

Methylated BCAT1/IKZF1 ctDNA reflects treatment response, offering a tool for personalised treatment.