Abstract
Background: In most countries, participation in colorectal cancer (CRC) screening programs with the immunological fecal occult blood test (iFOBT) is low. Mutations of RAS and BRAF occur early in colorectal carcinogenesis and “liquid biopsy” allows detection of mutated circulating tumor DNA (ctDNA). This prospective study aims to evaluate the performance of RAS and BRAF-mutated ctDNA in detecting CRC and advanced adenomas (AA). Methods: One hundred and thirty patients who underwent colonoscopy for suspicion of colorectal lesion were included and divided into four groups: 20 CRC, 39 AA, 31 non-advanced adenoma and/or hyperplastic polyp(s) (NAA) and 40 with no lesion. Mutated ctDNA was analyzed by droplet digital PCR. Results: ctDNA was detected in 45.0% of CRC, in 2.6% of AA and none of the NAA and “no-lesion” groups. All patients with stage II to IV mutated CRC had detectable ctDNA (n = 8/8). Among the mutated AA, only one patient had detectable ctDNA (4.3%), maybe due to limited technical sensitivity or to a low rate of ctDNA or even the absence ctDNA in plasma. Specificity and sensitivity of KRAS- and BRAF-mutated ctDNA for the detection of all CRC and AA were 100% and 16.9%, respectively. Conclusions: ctDNA had high sensitivity in detection of advanced mutated CRC but was unable to sensitively detect AA. ctDNA analysis was easy to perform and readily accepted by the population but requires combination with other circulating biomarkers before replacing iFOBT.
Highlights
Colorectal cancer (CRC) is the third most common cancer worldwide
colorectal cancer (CRC). circulating free DNA (cfDNA) level was higher in CRC patients compared to patients with normal colonoscopy, but no difference was observed for patients with AA or non-advanced adenoma and/or hyperplastic polyp(s) (NAA) versus patients with normal colonoscopy
Patients were divided into 4 groups: patients with CRC (“CRC” group), patients with at least one AA (“AA” group), patients with non-advanced adenoma(s) and/or hyperplastic polyp(s) (“NAA” group), and patients with no colorectal lesion
Summary
Colorectal cancer (CRC) is the third most common cancer worldwide. It represents 9% of all cancers with 1,400,000 new cases and 700,000 deaths per year, and it is the fourth most common cause of cancer death. AA and early CRC are usually asymptomatic, but frequently entail occult bleeding which may be detected by immunochemical fecal occult blood test (iFOBT). Participation in colorectal cancer (CRC) screening programs with the immunological fecal occult blood test (iFOBT) is low. Mutations of RAS and BRAF occur early in colorectal carcinogenesis and “liquid biopsy” allows detection of mutated circulating tumor. This prospective study aims to evaluate the performance of RAS and BRAF-mutated ctDNA in detecting CRC and advanced adenomas (AA). Methods: One hundred and thirty patients who underwent colonoscopy for suspicion of colorectal lesion were included and divided into four groups: 20 CRC, 39 AA, 31 non-advanced adenoma and/or hyperplastic polyp(s) (NAA) and 40 with no lesion.
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