[Jinyun Exclusive Interview] The Cutting-Edge Technology He Studies Brings New Hope to Cancer Patients
Introduction: Recently, a Jinyun reporter visited ProteinT, and the [These People, This City] feature conducted an exclusive interview with Dr. Li Jie, founder of ProteinT. Over his 8 years rooted in Tianjin, he has led ProteinT to continuously make technological breakthroughs in the fields of proteomics and multi-omics, and has been working tirelessly on the clinical application of new technologies. The following is a full reprint of ＂[These People, This City] The Cutting-Edge Technology He Studies Brings New Hope to Cancer Patients＂ More than 100 years ago, humans discovered cancer, and since then, humanity has been committed to finding ways to conquer it. To this day, medicine has made countless advances in cancer research, yet for most people, cancer remains an incurable disease. On the other hand, cardiovascular and cerebrovascular diseases have quietly ＂risen,＂ and in recent years their harm to humanity has surpassed cancer. These two types of diseases are together called the two great killers of human health. Twenty-one years ago, after completing postdoctoral training at the National Institutes of Health (NIH) in the United States, Dr. Li Jie, then an associate professor at Tianjin Medical University, began research on translating proteomics into clinical products, carrying the original aspiration of applying more advanced life sciences to clinical practice. It was there that he first encountered proteomics research. In 2014, Li Jie returned to China to start a business as a leader in international proteomics, pushing gene-protein-metabolite multi-omics centered on proteomics toward clinical application in cancer and cardiovascular and cerebrovascular diseases.Li Jie (right) in the laboratory If the treatment process of a disease is compared to a battle, then the role of proteomics is like an ＂intelligence agent＂—it can more precisely reflect the overall condition of the disease, providing enormous help for doctors to understand the true condition and implement precision treatment. In the future, the widespread application of proteomics may bring disruptive changes to the diagnosis and treatment of cancer and cardiovascular and cerebrovascular diseases.Gene + Protein: Adding Wings to a Tiger In 1998, Li Jie graduated with a doctorate from Tianjin Medical University and became a neurosurgeon at Tianjin General Hospital. After accumulating several years of clinical experience, in 2001 Li Jie chose to go to the United States to continue researching cutting-edge technologies for disease treatment and diagnosis. After working at the National Institutes of Health (NIH) for 7 years, he entered the Department of Pathology at Yale University School of Medicine to work. At that time, Yale researchers were working on translating genomics applications to diseases, and Dr. Li Jie was responsible for gene sequencing and the pathology library, deeply participating in genomics, which was then at the industry＇s forefront. Scientists had once speculated that genes might hold the ultimate secrets of the human body. After more than a decade of research, human gene sequencing made major progress, but at this point scientists discovered a new field of research—proteomics. ＂You can understand genes as numbers, and decoding genes is equivalent to reading numbers, but what controls the genes behind them is proteins. It is proteins that make up the coding of genes. Proteins are the truly active, foundational substances of all life, able to reflect health and disease more directly,＂ said Dr. Li Jie. Constrained by technical conditions, it was not until 2012, when high-throughput protein quantitative sequencing technology emerged, that proteomics research had the conditions to translate toward disease. Since then, as genomics technologies entered clinical application, the concept of ＂precision medicine＂ based on omics technologies began to gain popularity. Analyzing the human body with omics technologies can be refined down to every single molecule within a cell. The clinical application of genomics began with tumor diseases. According to calculations by the ＂Journal of Political Economy＂ and the U.S. Department of Labor, every 1% reduction in cancer mortality can bring about 695 billion U.S. dollars in economic value. However, relying solely on genomics to find targeted drugs for cancer patients yields a suitability rate of only 8.33%; yet once proteomics is added, the suitability rate of targeted drugs for patients can rise to 84%. ＂Although the efficacy of the drugs still requires later observation, this increase in percentage is still of great significance,＂ said Dr. Li Jie.Returning to China to Start a Business: Both Emotionally and Rationally, Choosing Tianjin Li Jie is one of the earliest researchers worldwide to translate proteomics toward clinical practice. During his time at Yale, he gave an academic report on the theme of proteomics to a visiting Chinese delegation. After hearing Li Jie＇s report, many domestic experts and officials extended sincere invitations to him, hoping he would return to China to develop his career. In 2014, Li Jie formally returned to China to start a business as a ＂leader in international clinical proteomics,＂ and after careful consideration, chose to locate the company in Tianjin. Li Jie was born in Shanxi, came to Tianjin with his parents at the age of 2, and has lived in Tianjin for nearly 30 years since. He is familiar with this city, and the Tianjin dialect makes him feel at home. But his choice to start a business in Tianjin was not merely emotional: ＂Tianjin has a very deep foundation in medicine. Throughout the country, you cannot find a second city with as many specialized hospitals as Tianjin—neurosurgery, thoracic, oncology, obstetrics and gynecology, pediatrics, and so on. For doing research, these specialized hospitals can provide a large number of samples, which is very attractive. In addition, Tianjin＇s entrepreneurial environment is also very friendly, allowing me to focus on research.＂ In 2014, ProteinT (Tianjin) Biotechnology Co., Ltd. was formally established, and in 2016 it was approved as a national high-tech enterprise. In the company＇s English name ＂Protein T,＂ ＂Protein＂ means protein, and one of the meanings of ＂T＂ represents ＂Tianjin.＂ The company＇s first goal after establishment was to break through the ＂last mile＂ of applying proteomics technology to clinical practice. Applying it to clinical practice requires two conditions: first, accumulating a large number of samples for each disease type for comparison, and second, reducing the requirements for the test sample. ＂In the early days of proteomics testing, the sample volume required was relatively large, and it had to be fresh,＂ Li Jie said, gesturing a circle the size of an egg yolk with his fingers. ＂But now the trend in hospital pathology sampling is to take smaller and smaller samples, minimizing trauma to the patient. The hospital first uses part of the sample taken, and only then can it be used for research. We spent 4 years completing the technological breakthrough. Now we only need a sample 5 micrometers thick and the size of a soybean to complete testing, and it doesn＇t need to be fresh.＂ In 2018, ProteinT＇s proteomics technology met clinical standards. In the same year, ProteinT established a medical laboratory with Grade I medical institution qualifications, and ProteinT began to truly serve clinical cases, opening a new window for the treatment of cancer and cardiovascular and cerebrovascular diseases.The Tianjin Key Laboratory of Clinical Multi-omics led by ProteinTDelivering ＂Exclusive Intelligence＂ to Doctors Know yourself and know your enemy, and you will never be defeated in a hundred battles. This saying applies not only to the battlefield but also to clinical diagnosis and treatment. For a long time, doctors treating tumors have inevitably had the feeling of ＂opening a blind box＂—whether a medication works, on the one hand depends on experience, and on the other on luck. The clinical finding of a high correlation between alpha-fetoprotein (AFP) and cancer was also an empirical conclusion derived retrospectively through comparison of large numbers of samples. But the human body is known to contain tens of thousands of proteins, and using the method of observing AFP to search for other tumor markers is like fishing for a needle in the ocean. The significance of the clinical application of proteomics is to turn the blind box into a glass box. The ＂T＂ in the company＇s English name has another meaning—＂Target,＂ meaning helping doctors find the target, so that doctors can diagnose and prescribe with clarity. When initially cooperating with hospitals, doctors still held some skepticism about ProteinT＇s testing, but in less than 1 year, ProteinT＇s reputation spread within the field. Since 2019, ProteinT＇s annual number of test samples has been running at full capacity. ProteinT produces two test reports for each sample, one genomic report and one proteomic report, with accompanying medical interpretations of the reports. ＂Before the application of omics technologies, different people with the same disease used the same medication, but with omics reports, we can identify the individualized differences of the disease, allowing patients to get the maximum benefit at the minimum cost,＂ said Li Jie. Some patients can be ＂brought back from the brink＂ because of a single omics report. ProteinT once conducted testing for a male lung cancer patient in his 70s. Before the proteomics test, his genetic test was negative, meaning there was no suitable targeted drug for him. So he could only receive conventional treatment, and after radiotherapy and chemotherapy, the tumor actually grew larger. As a Stage III cancer patient, he had essentially been sentenced to ＂death.＂ However, the proteomics test report revealed his individualized differences—there was a defect in one of his oncogenic pathways, and there happened to be a drug on the market that targeted it. After two courses of medication, the patient had basically recovered, and four or five years have passed since without recurrence.One Small Kit Benefits More People Blood testing has long been a major bottleneck in the clinical application of proteomics. Human blood contains about 10,000+ proteins, and a small number of dozens of proteins account for 99.9% of the total protein in blood; these are called ＂high-abundance proteins＂ and are interfering factors in testing. Dr. Li Jie calls these proteins a mountain, while the proteins that truly have testing significance—though numerous in variety, sparse in number—are called by Li Jie the small grass on the mountain. In 2021, Li Jie led his team to a breakthrough in the ＂high-abundance depletion＂ technology, which he vividly likened to ＂removing the mountain to see only the grass.＂ This technology is especially significant in early cancer screening, as it will help testers more keenly capture those proteins with tumor marker properties. ＂Previously we could only observe 400 proteins in the blood, but now we can monitor more than 4,000, increasing our ability to find tumor markers tenfold. This testing level is also first-class internationally. Moreover, we use very little blood—only 20 microliters, about 1 drop, and there is only one step; the fewer the steps, the better the stability of the technology,＂ said Li Jie. ProteinT is currently actively applying for the relevant industry licenses. Once approved, proteomics testing will be able to be incorporated into the hospital examination system, and ProteinT will also become one of the first institutions in the world to complete the clinical translation of proteomics. ＂Our current testing is still a laboratory-developed test (LDT), and testing can only be carried out in our medical laboratory. This is very inconvenient, and our testing capacity is limited—at full capacity we can only test a few thousand samples a year. After obtaining the license, we will launch proteomics kits, so doctors can do testing in-house, and the number of tests will increase substantially. If the application of genomics technology started first in the United States, I hope the application of proteomics technology can start from China, starting from Tianjin.＂
