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Identification of Early Cancer through Peripheral Blood Mature Red Blood Cells!  Chinese Scholars Reveal Cancer-Related Large DNA Fragments within Red Blood Cells for the First Time

January 12, 2023

Liquid biopsy technology is the new direction for early screening and diagnosis of cancer recognized worldwide. The mainstream of liquid biopsy is the detection of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and exosomes, which are biomarkers derived from plasma or serum. Red blood cells are usually removed during sample processing because it is traditionally believed that they do not contain DNA.

However, the application of liquid biopsy in early cancer screening and diagnosis faces two major bottlenecks, which limit the further improvement of its detection sensitivity and accuracy:

• In early-stage cancer, the content of ctDNA, CTCs, and other biomarkers in serum and plasma is low, making enrichment difficult.

• The specificity and sensitivity of biomarker detection are insufficient to meet the requirements for early cancer detection.

One of the key conclusions of the latest Pathfinder study by the US cancer screening leader, GRAIL, in 2022 is that the sensitivity of early tumors remains a major issue, which directly leads to the target of shifting the stage forward not being achieved. The ability to detect common tumors such as breast, colon, lung, cervical, and prostate cancers in their early stages is weak and cannot replace the cancer screening methods recommended by existing guidelines.

So, do red blood cells, which account for as much as 45% of blood, contain DNA fragments? Can red blood cells become a new sample source for liquid biopsy technology and be applied to early cancer screening and diagnosis?

Chinese researchers have recently given an exciting answer: Yes!

Breakthrough innovative research

On January 4, 2023, Dr. Qihan Chen from the Medical School of Nanjing University, Dr. Hongwei Liang from the School of Life Sciences of China Pharmaceutical University, and Dr. Naixin Liang from Beijing Union Medical College Hospital, and Dr. Zichen Jiao from Nanjing Drum Tower Hospital and other researchers published a paper entitled “Mature Red Blood Cells Contain Long DNA Fragments and Could Acquire DNA from Lung Cancer Tissue” in the journal Advanced Science (IF=17.5).

The study first confirmed that mature human red blood cells contain long fragments of DNA, most of which are more than 1000bps, and many exceed tens of thousands. The study also found that there were significant differences in the DNA characteristics of red blood cells between normal people and patients with benign and malignant nodules in the lungs. The DNA of early lung cancer patients’ red blood cells could detect common tumor mutations in their tumor tissue, demonstrating extremely high sensitivity.

Although these results are still relatively early-stage research, long fragments of DNA usually contain more complete biological information than small fragments. The lifespan of red blood cells, which is up to 120 days, also helps to preserve these tumor biological information from rapid metabolic clearance. Therefore, red blood cells have a high potential application value in the early diagnosis of cancer.

Professor David Kerr, a Fellow of the Royal Society and former President of the European Society for Medical Oncology (ESMO) at the University of Oxford Medical School, expressed surprise and anticipation for this groundbreaking study: “Liquid biopsy is one of the most promising cancer diagnostic methods to have entered the clinic in recent years. However, in early stage cancers, the amount of ctDNA found in serum or plasma are very low and can be difficult to enrich. This can lead to insufficient sensitivity and specificity for early cancer detection. I am glad to see this novel study present intriguing evidence about the presence of long DNA fragments in mature RBCs, and that such fragments can be acquired from lung cancer tissue. If these observations can be clinically validated further, this finding may represent a breakthrough in the field of liquid biopsy to aid diagnosis and follow up of cancer patients.”

Liquid biopsy enters a new era

This study provides a new source of cancer biomarkers: red blood cells. This is a breakthrough in terms of cognition and a new exploration of the underlying technology of liquid biopsy. Early screening and diagnosis of cancer is one of the main application areas of liquid biopsy, and this market is growing rapidly. It is expected that the Chinese market will exceed RMB 150 billion by 2025.

MBMbio has developed the world’s first red blood cell liquid biopsy technology platform, which can break through the barriers of cf/ctDNA technology. It has been proven that long DNA fragments can be extracted from red blood cells at 50-100 times higher levels than cfDNA in the same volume of peripheral whole blood, with tremendous conversion potential and clinical value.

MBMbio plans to use this new technology to try to solve the world’s problem of early diagnosis of lung cancer (the differentiation diagnosis of benign and malignant nodules less than 1 cm in size in the lung). Despite the increasing popularity of various auxiliary diagnostic methods, the early diagnosis rate of lung cancer in China is still only 18%. There are over 100 million people in China with lung nodules, and nodules less than 1 cm in size account for 90% of this population. However, existing ctDNA detection has extremely low sensitivity for this population, with a positive predictive value (ppv) of only 4.4% to 10%. MBMbio’s first clinical study using the red blood cell liquid biopsy platform showed a ppv of more than 50% for nodules less than 1 cm in size, greatly improving the detection rate of early-stage tumors.


About MBMbio

Founded in 2016, MBMbio aims to Bridging Global Innovation in Precision Medicine. The team is dedicated to becoming a world-class commercialization platform for precision healthcare products and services, with a focus on novel cancer biomarker discovery and product development using MBMbio’s proprietary AI digital pathology and Red Blood Cell liquid biopsy platforms. MBMbio was named a Top 30 Enterprise in the 2020 China Innovation & Entrepreneurship Competition, which is China’s largest innovation and entrepreneurship competition organized by the Ministry of Science and Technology, Ministry of Finance and other national ministries and organizations.

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Mature Red Blood Cells Contain Long DNA Fragments and Could Acquire DNA from Lung Cancer Tissue. Advcanced Science. Volume 10, Issue 7


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