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Novel Enrichment Technology Indicates High Performance for Multi-Cancer Detection

By LabMedica International staff writers
Posted on 10 Feb 2020
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Image: The flexible NextSeq 550 System offers a seamless transition between high-throughput sequencing and array scanning (Photo courtesy of Illumina).
Image: The flexible NextSeq 550 System offers a seamless transition between high-throughput sequencing and array scanning (Photo courtesy of Illumina).
Breast, lung, pancreatic, and prostate cancer make up 41% of the cancer incidence in the USA. Early detection and a deep understanding of each cancer remain critical for implementing the highest quality of care.

Tissue biopsy is invasive, and screening methods are limited for many forms of cancer and often fall short of capturing the complete genomic landscape. A new liquid biopsy combined with 5-hydroxymethyl cytosine (5hmC) profiling provides a detailed picture of the genomic landscape and identify potential biologic pathways that may be driving tumor progression.

Scientists working at Bluestar Genomics (San Francisco, CA, USA) and their academic colleagues obtained cancer and control patient cell-free DNA (cfDNA) cohorts from multiple sites consisting of 48 breast, 55 lung, 32 prostate and 53 pancreatic cancer subjects. In addition, a control cohort of 180 subjects (non-cancer) was employed to match cancer patient demographics (age, sex and smoking status) in a case-control study design. Plasma was isolated from whole blood specimens obtained by routine venous phlebotomy at the time of subject enrollment.

For both cancer and control subjects, whole blood was collected in Cell-Free DNA BCT tubes (Streck, La Vista, NE, USA) and cfDNA was isolated using the QIAamp Circulating Nucleic Acid Kit (QIAGEN, Germantown, MD, USA), excepting the omission of carrier RNA during cfDNA extraction. Sequencing library preparation and 5hmC enrichment was performed and DNA sequencing was performed with 75 base-pair, paired-end sequencing using a NextSeq550 instrument (Illumina, San Diego, CA, USA).

The team executed the study using multiple cell-free DNA samples to measure 5hmC profiles from patients with breast, lung, pancreatic, and prostate cancer. When used in conjunction with machine learning-based classification methods, their novel enrichment technology exhibited high performance in classifying these cancer samples with Area Under the Curve (AUC) measures of 0.89, 0.84, 0.95 and 0.83, respectively. The majority of the breast and pancreatic cancer samples were stage 1 or stage 2, validating Bluestar Genomics' potential to aid clinical decision making and detect cancer when treatment is most effective.

Kelly Bethel, MD, Chief Medical Officer, Bluestar Genomics, said, “There are significant limitations in screening for various cancers. Our data outperforms screening PSA testing, the current standard of care screening blood test for prostate cancer. Detection of small early malignancies is challenging by usual imaging methods, and our platform technology also demonstrates the ability to detect the presence of malignant tumors smaller than 2 cm. Overall, these findings suggest a clinical path toward early detection as part of a multi-cancer screening test.” The study was presented at the PMWC 2020 Silicon Valley conference on January 23, 2020, Santa Clara, CA, USA.

Related Links:
Bluestar Genomics
Streck
QIAGEN
Illumina



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