Circulating Free Tumor DNA in Patient Plasma is a Near-Perfect Marker for Metastatic Spread of Colorectal Cancer: A Study on 165 Patients Undergoing Surgical Treatment
Abstract
It is a primary aim of this tudy to investigate occurrence of cfDNA as potential marker of regional and distant metastatic progression of colorectal cancer and to trace the source of cfDNA in patients undergoing surgery treatment at different levels of radicality. METHODS: In a group of 165 patients in various stages of the disease tissue samples were initially acquired either as biopsies or resections.
Samples were tested for a presence of the most frequent somatic colorectal cancer mutations within APC, BRAF, KRAS, TP53 and PIK3CA genes. In addition, multiple plasma samples (n=789) were acquired over a time period covering (i) initial examination, (ii) immediately preceding a surgery (iv) post-surgery and (v) subsequent follow-up.
Cell-free tumor DNA was traced in patient plasma by targeting mutations previously detected in tumor tissue. RESULTS: Over 70% of colorectal cancer patients harbor somatic mutations in a small panel of genes including APC, BRAF, KRAS, TP53 and PIK3CA.
These mutations can be used as tumor-specific tags for detection of cfDNA. Presence of cfDNA is correlated to the disease stage through a combined effect of tumor size with local and distant metastases.
Occurence of cfDNA is not correlated to the levels of tumor biomarkers (CEA, CA19-9), thus could serve as an alternative. CONCLUSION: Due to insufficient sensitivity (out of 40 patients with advanced disease only 20 exhibited cfDNA) cfDNA is not applicable for screening of colorectal cancer progression.
Due to high specificity (out of 24 patients exhibiting cfDNA 20 had clinically confirmed progression of the disease) cfDNA is applicable as a predictive marker of colorectal cancer progression.