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Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
Longitudinal Circulating Tumor DNA Profiling in Metastatic Colorectal Cancer During Anti-EGFR Therapy
Wentao Yang1,2, Jianling Zou1,2, Ye Li2,3
1Department of Gastrointestinal Medical Oncology Fudan University Shanghai Cancer Center, Shanghai, China.
Background:
Metastatic colorectal cancer (mCRC) is a heterogenous disease with limited precision medicine and targeted therapy options. Monoclonal antibodies against epidermal growth factor receptor (EGFR) have been a crucial treatment option for mCRC. However, proper biomarkers for predicting therapeutic response remain unknown. As a non-invasive test, circulating tumor DNA (ctDNA) is appropriately positioned to reveal tumor heterogeneity and evolution, as it can be used in real-time genomic profiling. To evaluate the significance of ctDNA in monitoring the dynamic therapeutic response and prognosis of mCRC, we detected the baseline and dynamic changes of ctDNA in mCRC patients receiving anti-EGFR therapies.
Methods:
A single-center study was conducted retrospectively. Plasma samples from mCRC patients who received anti-EGFR therapies were collected at baseline and continuous treatment points. The ctDNA was extracted and sequenced with a target panel of tumor-related genes via next-generation sequencing (NGS). Clinical information was also collected and analyzed.
Results:
We conducted dynamic sampling of 22 mCRC patients, analyzed 130 plasma samples, obtained a baseline genomic mutation profile of the patients. In total, 54 variations were detected in 22 plasma samples, with a positive rate of 77.3% (17/22). TP53 was the most mutated gene (59.1%, 13/22), followed by APC (18.2%, 4/22). There was a high concordance rate of genomic characteristics between the tumor tissue test by polymerase chain reaction and ctDNA test by NGS. The mutation discrepancy increased with an extended course of treatment. During remission TP53 and APC were the most frequently decreased clonal mutations and KRAS, NRAS, ERBB2 and PIK3CA were the most decreased subclonal mutations. Both mutation types were increased during progression. The ctDNA decreased earlier than did the responses of computed tomography and traditional tumor markers (carbohydrate antigen 19-9 and carcinoembryonic antigen [CEA]). Lactate dehydrogenase level (P = 0.041), CEA level (P = 0.038), and primary lesion site (P = 0.038) were independent risk factors that influenced overall survival. Moreover, patients with RAS mutations tended to have a worse prognosis (P = 0.072).
Conclusions:
This study demonstrates that ctDNA is a promising biomarker for monitoring the dynamic response to treatment and determining the prognosis of mCRC.
Insights
Circulating tumor DNA (ctDNA) effectively monitors treatment response and predicts prognosis in metastatic colorectal cancer (mCRC) patients receiving anti-EGFR therapies. This non-invasive test reveals tumor dynamics earlier than traditional markers.
Area of Science:
- Oncology
- Genomics
- Molecular Diagnostics
Background:
- Metastatic colorectal cancer (mCRC) presents heterogeneity with limited targeted therapy options.
- Biomarkers for predicting therapeutic response to anti-EGFR therapies in mCRC are needed.
- Circulating tumor DNA (ctDNA) offers non-invasive real-time genomic profiling for tumor heterogeneity and evolution.
Purpose of the Study:
- To evaluate the significance of ctDNA in monitoring dynamic therapeutic response.
- To assess the prognostic value of ctDNA in mCRC patients undergoing anti-EGFR therapy.
Main Methods:
- Retrospective single-center study analyzing 130 plasma samples from 22 mCRC patients.
- Next-generation sequencing (NGS) of ctDNA using a targeted gene panel.
- Collection and analysis of clinical information and traditional tumor markers.
Main Results:
- 77.3% of patients had detectable ctDNA at baseline, with TP53 and APC as the most frequently mutated genes.
- ctDNA mutation dynamics correlated with treatment response, decreasing during remission and increasing during progression.
- ctDNA levels decreased earlier than computed tomography and traditional tumor markers (CEA, CA19-9).
- Lactate dehydrogenase, CEA levels, and primary lesion site were independent risk factors for overall survival.
- RAS mutations suggested a trend towards worse prognosis.
Conclusions:
- ctDNA is a promising non-invasive biomarker for monitoring treatment response in mCRC.
- Dynamic ctDNA analysis provides valuable prognostic information for mCRC patients.
- ctDNA facilitates real-time genomic profiling to guide precision medicine strategies.
