Concordance between the tumor mutational status and circulating tumor DNA in patients with colorectal cancer

Abstract

Background. Circulating tumor DnA (ctDnA) may act as a potential biomarker for predicting disease progression in patients with colorectal cancer (CRC), which are radically cured or receiving chemotherapy.Objective: to evaluate the sensitivity of the investigated ctDnA detection assay and quantify the concordance of genomic alterations between ctDnA and matched primary tumor tissue of patients with CRC.Materials and methods. we included patients with histologically confirmed stage I–Iv CRC treated in n.n. Blokhin Cancer Research Center from 2016 to 2021. DnA was purified from tissue samples using QIAamp DnA formalin-fixed paraffin-embedded (ffPE) Tissue Kit (QIAgEn, germany). next-generation sequencing (ngS) technique was used to detect genetic mutations in primary tumor. ctDnA mutations were detected by droplet digital PCR.Results. The sensitivity of platform (assay) for detecting genetic alterations in tissue samples was 97.82 %; in ctDnA – 51.20 % for all stages and 64.5 % for stage Iv CRC. Across eight genes (KRAS, TP53, APC, PIK3CA, BRAF, FBXW7, MB21D2, and SMAD4) concordance between primary tumor and ctDnA was 69.4 % (95 % CI 62.2–76.0). Sensitivity for all stages is 51.2 % (95 % CI 45.8–56.6), for metastatic CRC 64.5 % (95 % CI 53.3–74.5). The concordance across all genes was 65.4 % (95 % CI 57.1–73.1) and 83.8 % (95 % CI 69.6–92.9) for stage I–III and stage Iv CRC, respectively. The concordance rate between ctDnA and primary tumor tissue for KRAS alterations across all stages and stage Iv CRC was 78.3 % (95 % CI 66.7–87.3) and 90.9 % (95 % CI 64.7–99.0), respectively. with increasing tumor stage (T), the number of matches raised across all genes with the highest number observed in nx category.Conclusion. The study indicates high concordance between tumor tissue and ctDnA, especially for KRAS and BRAF genes in patients with metastatic CRC, suggesting the clinical utility of ctDnA testing as a minimally invasive method and alternative to tissue biopsy.