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CancerSEEK Promises Earlier Detection of Cancer

Liquid biopsy test assesses the levels of circulating proteins and mutations in cell-free DNA
12 Feb 2018
Translational research

Researchers from the John Hopkins Kimmel Cancer Center in Baltimore, Maryland, USA reported on 18 January 2018 in Science results of blood test, called CancerSEEK, applied to 1,005 patients with non-metastatic, clinically detected eight common cancer types: ovarian, liver, stomach, pancreatic, oesophageal, colorectal, lung, and breast. The test assesses the levels of circulating proteins and mutations in cell-free DNA and was positive in a median of 70% of these eight cancer types. 

The study authors wrote in background that earlier detection of cancer is key in reducing cancer-related deaths. The first component of CancerSEEK determines mutations in cell-free DNA. The second component is determining levels of protein biomarkers. The algorithm in the study then used machine-learning tools and statistical analyses to determine the median sensitivity and specificity of the test. 

With purified DNA from plasma, the researchers amplified the sample with multiplex–polymerase chain reaction using a robust 61-amplicon panel that had the ability to detect rare mutations. The 61 primer pairs were designed to amplify 66 to 80 base-pair segments of the DNA in regions of interest from 16 genes. The amplified products were uniquely labelled with a DNA barcode and were matched to reference sequences present in the Catalogue of Somatic Mutations in Cancer dataset or ones that were predicted to be inactivating mutations in tumour suppressor cells. 

The second component of the test is determining levels of protein biomarkers. The reason for incorporating this step is that early-stage tumours do not release detectable circulating tumour DNA. The eight proteins measured are CA 125, CEA, CA 19-9, prolactin, hepatocyte growth factor, osteopontin, myeloperoxidase, and tissue inhibitor of metalloproteinases 1. 

For the study, the researchers recruited 1,005 patients with median age at diagnosis of 64 years. The most common stage of disease at presentation was stage II (49%), 20% of patients had stage I cancer, and 31% of patients had stage III disease. The study also included a control group of 812 healthy individuals with median age of 55 years, who had no history of cancer. 

The median overall sensitivity of the test was 70% for the eight common cancers. The sensitivities of CancerSEEK ranged from 69% to 98% for the detection of five cancer types (ovarian, liver, stomach, pancreatic, and oesophageal) for which there are no screening tests available for average-risk individuals.  

The median sensitivity of CancerSEEK was 73% for stage II cancers, 78% for stage III cancers, and 43% for stage I cancers. For stage I cancers, the highest sensitivity was for liver cancer (100%), and the lowest was for oesophageal cancer (20%). 

The specificity of CancerSEEK was more than 99%. The study team pointed out that only 7 of 812 healthy controls scored positive. 

In addition, CancerSEEK localised the cancer to a small number of anatomic sites in a median of 83% of the patients. 

There are several limitations of this study, the key one is that patients with known cancers were enrolled. The vision would be to use the test in asymptomatic individuals to screen for cancer. The Johns Hopkins collaborates in that regard with the Geisinger Health System in Pennsylvania; they have already started to use the test on blood samples from female volunteers aged between 65 and 75 years who have never had cancer. This 5-year study of up to 50,000 women is funded by a private philanthropic group, The Marcus Foundation. 

The current test is not ready for clinic yet. However, the study findings published in Science lay the conceptual foundation for a single, multi-analyte blood test for early detection of many types of cancers. The researchers concluded that for establishing the clinical utility of CancerSEEK, prospective studies of all incident cancer types in a large population are required. 


Cohen JD, Li L, Wang Y, et al. Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science; Published online 18 January 2018. pii: eaar3247. DOI: 10.1126/science.aar3247

Last update: 12 Feb 2018

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