Evaluation of serum CEA, CYFRA21-1 and CA125 for the early detection of colorectal cancer using longitudinal preclinical samples

Abstract

Background:Blood-borne biomarkers for early detection of colorectal cancer (CRC) could markedly increase screening uptake. The aim of this study was to evaluate serum carcinoembryonic antigen (CEA), CYFRA21-1 and CA125 for the early detection of CRC in an asymptomatic cohort.Methods:This nested case–control study within UKCTOCS used 381 serial serum samples from 40 women subsequently diagnosed with CRC, 20 women subsequently diagnosed with benign disease and 40 matched non-cancer controls with three to four samples per subject taken annually up to 4 years before diagnosis. CEA, CYFRA21-1 and CA125 were measured using validated assays and performance of markers evaluated for different pre-diagnosis time groups.Results:CEA levels increased towards diagnosis in a third of all cases (half of late-stage cases), whereas longitudinal profiles were static in both benign and non-cancer controls. At a threshold of >5 ng ml−1 the sensitivities for detecting CRC up to 1 and 4 years before clinical presentation were 25% and 13%, respectively, at 95% specificity. At a threshold of >2.5 ng ml−1, sensitivities were 57.5% and 38.4%, respectively, with specificities of 81% and 83.5%. CYFRA21-1 and CA125 had no utility as screening markers and did not enhance CEA performance when used in combination. CEA gave average lead times of 17–24 months for test-positive cases.Conclusions:CEA is elevated in a significant proportion of individuals with preclinical CRC, but would not be useful alone as a screening tool. This work sets a baseline from which to develop panels of biomarkers which combine CEA for improved early detection of CRC.

Circulating lncRNA SNHG11 as a novel biomarker for early diagnosis and prognosis of colorectal cancer

“…studied factors associated with false‐positive FIT results, including male sex, older age, obesity, smoking, aspirin use and newly detected nonneoplastic bowel disease. The currently identified tumour biomarkers, such as CEA, CA19‐9 and CA12‐5, have not shown sufficient sensitivity and specificity for the detection of precancerous lesions and early‐stage tumour formation . Thus, lncRNAs have gained much attention as noninvasive biomarkers for improved CRC screening methods.…”

A versatile quantitation platform based on platinum nanoparticles incorporated volumetric bar-chart chip for highly sensitive assays

“…When different concentrations of CEA was spiked in serum, the ink bar charts exhibited the similar detection results as that obtained from the buffer, indicating that serum matrices do not interfere significantly with the sensitivity. The cutoff value of CEA for colorectal cancer in serum is 5 ng/mL (Thomas et al, 2015). Thus, the detection limit of the HCR amplified 3V-Chip is well within the range of clinical relevance for colorectal cancer monitoring.…”

CEACAM Gene Family: A Circuitous Journey towards Metastasis in Breast Cancer

“…Gold and Freedman [14], were the first to discover CEACAM5 in the blood of colon cancer patients and further research established that its Overexpression in numerous malignancies is usually correlated with poor prognosis, and increased mortality [8,14,15]. In prostate and in colorectal cancers, CEACAM 5 over-expression was documented as an excellent tumor biomarker [16,17], although it may not be useful as a standalone early screening tool for CRC [18]. Additional evidence about the Overexpression of CEACAM6 in CRC is also associated with increased invasiveness and liver metastasis [19].…”