Circulating tumor DNA detectable in early- and late-stage colorectal cancer patients

Abstract

Characterization, diagnosis, and treatment of colorectal cancers (CRC) is difficult due to limited biopsy information, impracticality of repeated biopsies, and cancer biomarker fallibility. Circulating tumor DNA (ctDNA) has recently been investigated as a non-invasive way to gain representative gene mutations in tumors, in addition to monitoring disease progression and response to treatment. We analyzed ctDNA mutations and concentrations in 47 early- and late-stage CRC patients using a targetted sequencing approach using a panel that covers 50 cancer-related genes. ctDNA mutations in 37 genes were identified in 93.6% of the patients (n=47). The results showed that TP53, PIK3CA, APC, and EGFR were the most frequently mutated genes. Stage IV patients had significantly higher ctDNA concentration than Stage I patients, and increased ctDNA concentration correlated with increased tumor size. Additionally, ctDNA detection was found to be a greater predictor of disease when compared with five known commonly used tumor biomarkers. The present study supports the use of ctDNA as a liquid biopsy to gain clinical tumor information that may facilitate early diagnosis and treatment and improve CRC patient prognosis.

Detection of mutations in circulating cell‐free DNA in relation to disease stage in colorectal cancer

“…22 Considering that there is room for improvement in study design, different studies confirmed that ctDNA concentrations increase with tumor size and cancer stage. 23 This is consistent with the analysis of Bettegowda et al, who revealed a 47% sensitivity of KRAS mutation detection in cfDNA in stage I CRC patients, which increased to 87% in stage IV cancer. 6 Diehl et al reported that the number of mutant APC gene molecules in the circulation of CRC patients depends on tumor stage being as little as 0.01% in stage I patients.…”

“…In contrast to other isolation kits, such as the QIAamp Circulating Nucleic Acid kit, the QIAamp DNA Blood Midi kit is reported to be inferior regarding the isolation of short‐fragmented ctDNA . Considering that there is room for improvement in study design, different studies confirmed that ctDNA concentrations increase with tumor size and cancer stage . This is consistent with the analysis of Bettegowda et al, who revealed a 47% sensitivity of KRAS mutation detection in cfDNA in stage I CRC patients, which increased to 87% in stage IV cancer .…”

Perspectives of the Application of Liquid Biopsy in Colorectal Cancer

“…Quantifying ctDNA levels is closely related to cancer stage and tumor burden [77]. In a recent study that analyzed ctDNA in patients with CRC at different stages, Dr. Yang et al clarified that the ctDNA concentration in stage I patients was significantly lower than that in stage IV patients and that the ctDNA concentration was positively correlated with tumor size [78]. The observations and evaluations made during a study on the ctDNA analysis of patients receiving cetuximab suggested that the KRAS mutations in plasma detected by ctDNA were not detected by the radiological method until 10 months later [79].…”

Fractionated small cell‐free DNA increases possibility to detect cancer‐related gene mutations in advanced colorectal cancer

“…Recently, liquid biopsy, a process that identifies the presence of tumor genetic abnormalities using cell-free DNA (cfDNA), [9][10][11] circulating tumor cells, [12][13][14] and microRNA [15][16][17] that are extracted from body fluids such as plasma, serum, and urine, is gaining significant attention because of its less-invasive method to obtain genetic profiles. 11 In fact, and owing to its profound advantages, liquid biopsy is expected to be used clinically in cases such as early tumors detection, 18,19 tumor monitoring, [20][21][22][23][24] treatment effect prediction, 20 detection of drug resistance, and as a sensitivity marker. 18,21,[25][26][27][28] cfDNA normally exists in blood at a length of approximately 170 bp.…”