"Discover potential new targets for accurate treatment of HCC!" ——Chinese human proteome

Xinhua news agency, Beijing, March 2: "discovery of potential new targets for precise treatment of HCC!" -- three highlights of new breakthroughs in human proteomics in China Recently, there is another good news in the field of life science research! Chinese scientists published a breakthrough paper in the field of proteomic research of early HCC online through the international authoritative journal Nature, and found a potential new target for precise treatment of HCC What is proteomics? What is the great scientific value of this discovery? What does it mean for the next clinical treatment and drug research and development? The reporter came to the national protein science center in Beijing for the first time and interviewed the scientists of the paper team Proteomics: the "decoding artifact" to decipher the book of life Protein is the "last kilometer" of genetic information expression Proteome is the functional entity that constitutes the biological system and carries out the life process It is the direct material basis of human phenotype (physiological and pathological state) The concept of proteomics was put forward in 1995, which is another important research direction in the field of life science after genomics He Fuchu, the corresponding author of the paper and vice president of the Academy of Military Sciences, told reporters that proteomics research objects are more complex than genomes, and have greater challenges than genomics in experimental equipment, technical level, data mining ability and other aspects In recent years, the development of proteomics technology with chromatography and mass spectrometry as the core technology has driven the rapid growth of proteomics research in depth and breadth Qian Xiaohong, the corresponding author of the paper and researcher of the Academy of military medicine of the Academy of Military Sciences, said that through the early accumulation, China has reached the international advanced level in the technical ability of proteome expression spectrum analysis In the 2009 International proteome reference material evaluation, the technical ability of the national key Laboratory of proteomics is in the forefront of the world "The national key laboratory team of proteomics has developed an efficient proteomic pre classification and detection strategy, and has completed the mass spectrometry detection of 8000 human gene products within 12 hours, making it one of the fastest proteomic identification methods in the world." Qian Xiaohong said On the basis of the above technology accumulation, the Ministry of science and technology for the first time integrated 973 Plan, 863 plan and international cooperation plan After several years of demonstration, led by the State Key Laboratory of proteomics, Academy of military medicine, Academy of Military Sciences, officially launched the "China human proteome plan" in 2014 According to the introduction, by the end of 2018, the project has completed the construction of the deep coverage protein expression spectrum of early HCC and paracancerous tissue, diffuse gastric cancer and paracancerous tissue, intestinal gastric cancer and paracancerous tissue, lung adenocarcinoma and paracancerous tissue, pancreatic duct adenocarcinoma and paracancerous tissue, esophageal squamous cancer and paracancerous tissue, colon adenocarcinoma and paracancerous tissue, renal clear cell carcinoma and paracancerous tissue, with the data volume reaching 45.6tb At the high confidence level, 15553 kinds of human expression proteins were identified quantitatively, and the regulation of disease tissue signal network protein expression was obtained to realize the in-depth exploration of potential molecular markers and candidate targets Discover new target: the way to solve "the king of cancer" Liver cancer is often called "the king of cancer" Global cancer statistics in 2018 showed that the incidence rate of liver cancer worldwide ranked fifth in malignant tumors and second in mortality "How to accurately identify these poor prognosis early liver cancer patients and provide effective targeted treatment is the" hard bone "left by early diagnosis and early treatment of liver cancer in the world today." Fan Jia, the correspondence author and President of Zhongshan Hospital Affiliated to Fudan University, said In this study, according to the proteomic data of 101 cases of early HCC and matched paracancerous tissue samples, the researchers divided the currently clinically recognized patients with early HCC into three proteomic subtypes, and the patients with different subtypes have different prognosis characteristics, and need different treatment plans after operation Jiang Ying, the first author of the paper and researcher of Military Medical Research Institute of the Academy of Military Sciences, said that the first type of patients only need surgery to prevent over treatment; the second type of patients need surgery plus other auxiliary treatment; the third type of patients accounts for 30%, and the risk coefficient of recurrence and death after surgery is the largest The researchers found that in the proteomic data of the third group of patients, the cholesterol metabolism pathway was reprogrammed, and the high expression of candidate drug target cholesterol esterase had the worst prognosis risk By inhibiting the candidate drug target, cholesterol esterifying enzyme soat1, it can reduce the cholesterol level on the cytoplasmic membrane and effectively inhibit the proliferation and migration of tumor cells Opening up drug resistance: providing an important basis for the development of new anticancer drugs Liver cancer is a general term for different types of primary liver tumors in histology, including HCC, intrahepatic cholangiocarcinoma, hepatoblastoma, etc Among them, HCC accounts for about 90% of primary liver cancer From 2007 to 2017, there was only one chemotherapy drug for HCC, sorafenib, which was extremely scarce for such patients In recent years, several kinds of drugs have achieved good results in the clinical phase III study of HCC In addition, PD-1 inhibitors in immunotherapy have also entered the third phase of clinical experimental study in the treatment of HCC Fan Jia said that although the application of new drugs in clinical practice has brought hope and dawn to patients with HCC, these drugs are all targeted drugs for patients with advanced liver cancer, and the limited types and efficacy of drugs can not meet the clinical needs of patients with HCC "In order to improve the survival of patients with HCC and further expand the beneficiary population, it is urgent to develop new drug intervention targets for HCC, especially early treatment strategies." He Fuchu said The Chinese team of scientists explored a new way to conduct a comprehensive and in-depth proteomic analysis of a variety of human tumors represented by liver cancer through the "China human proteome program", and initially established the leading proteomics driven precision medicine in China He Fuchu said that compared with the first generation of genomics driven precision medicine, proteomics driven precision medicine belongs to the second generation of precision medicine, and the discovery and verification of proteomics for therapeutic targets of early liver cancer has opened a new stage of precision medicine This time, the researchers found that avamib, a small molecular inhibitor of soat1, showed good antitumor effect on human tumor xenotransplantation model of liver cancer patients, indicating that avamib is expected to be a potential target drug for the treatment of patients with poor prognosis The team also found a direct link between the reprogramming of cholesterol metabolism pathway and HCC for the first time, confirming the importance of cholesterol esterase in the development of HCC "With the help of massive proteomics data of patient group, we found that cholesterol esterase can be used for the classification, prognosis and targeted treatment of early liver cancer The high expression of cholesterol esterase protein in head and neck cancer, gastric cancer, prostate cancer, renal cancer and thyroid cancer is positively related to the poor prognosis of patients, which provides an important basis for the development of new anti-cancer drugs." He Fuchu said.