What are the most comprehensive methods for early diagnosis of liver cancer?

Statistics from the World Health Organization (WHO) in 2008 show that there are about 750,000 new cases of liver cancer and about 700,000 deaths worldwide each year. Hepatocellular carcinoma is the main type of liver cancer, accounting for more than 80% of liver cancer. More than half of the new cases and deaths worldwide occur in China each year, and it is a major disease that endangers the lives and health of the Chinese people. Due to the limitations of diagnostic methods, most patients with hepatocellular carcinoma are already in the middle and late stages when they seek medical treatment, and have lost the best treatment opportunity. Therefore, the discovery of new diagnostic markers for hepatocellular carcinoma, especially serum diagnostic markers, and timely and effective early detection, early diagnosis, and early detection are one of the keys to improving patient survival rates and reducing mortality rates. At present, the widely used tumor serum markers in routine clinical diagnosis and screening are basically serum protein markers. The main reason is that in addition to being non-invasive, tumor serum protein markers also have the advantages of requiring a small amount of serum sample (usually less than 100 microliters), no need for pre-treatment such as extraction and purification of blood samples, simple and easy to promote detection methods, automated rapid batch detection, high reproducibility, and low cost. DKK1 is a tumor serum protein marker with broad clinical application prospects.

On June 26, the research group of Qin Wenxin from the State Key Laboratory of Oncogenes and Related Genes of Shanghai Institute of Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, published a research paper titled "A Large-Scale Clinical Multicenter Study of Serum DKK1 Protein as a Diagnostic Marker for Liver Cancer" in the internationally renowned medical journal Lancet Oncology, proving that DKK1 protein can be used as a tumor marker for serum diagnosis of hepatocellular carcinoma. This is the first time that Chinese scientists have published a Phase II trial research paper on tumor serum protein markers with original innovation and independent intellectual property rights in a world-class clinical oncology and tumor translational medicine journal.

The person who led this research is Qin Wenxin, a researcher from the State Key Laboratory of Oncogenes and Related Genes. With the support of Academician Wang Hongyang, Director of the State Key Laboratory, Academician Yang Shengli and Academician Gu Jianren, Qin Wenxin and his research team first discovered and proved in 2003 that the secretory protein DKK1 (Dickkopf-1) is specifically highly expressed in various human tumors, including liver cancer, and its high secretory expression was detected in the culture supernatant of various human tumor cells and the serum of liver cancer patients. It can be used as a tumor serum protein marker for serum diagnosis of malignant tumors such as lung cancer, liver cancer, breast cancer, and cervical cancer. The above innovative findings have been applied for Chinese invention patents and international patents in 2005 and 2006 and have been made public at home and abroad. Subsequently, its research results have been widely verified by domestic and foreign laboratories. On this basis, in 2008, Qin Wenxin led the research team to design and carry out a large-scale clinical multicenter trial study on the use of tumor serum protein marker DKK1 for serum diagnosis of hepatocellular carcinoma. The clinical trial was jointly completed by four institutions, namely, Zhongshan Hospital Affiliated to Fudan University, Oriental Hepatobiliary Surgery Hospital of Second Military Medical University, First Affiliated Hospital of Soochow University and Shanghai Institute of Oncology of Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, which are important clinical centers and research bases for liver cancer in China. The research results were published in The Lancet Oncology in the form of "Fast Track". The main innovative findings are as follows: As a tumor serum protein marker, the sensitivity of DKK1 protein for the overall diagnosis of hepatocellular carcinoma can reach 69.1% and the specificity is 90.6%; in particular, the diagnostic sensitivity for early hepatocellular carcinoma (BCLC0+A) and small hepatocellular carcinoma (single less than 2 cm) can reach 70.9% and 58.5%, and the specificity is 90.5% and 84.7%, respectively; at the same time, DKK1 protein can make up for the lack of alpha-fetoprotein (AFp) in the diagnosis of hepatocellular carcinoma, and for negative alpha-fetoprotein (less than 20 ng/ The diagnostic sensitivity of DKK1 protein and alpha-fetoprotein is 70.4% and 90% respectively for hepatocellular carcinoma, and it can differentiate hepatocellular carcinoma from high-risk patients with chronic hepatitis B and cirrhosis who are positive for alpha-fetoprotein (higher than 20 ng/ml), with a sensitivity of 69.1% and a specificity of 84.7% respectively. The combined use of DKK1 protein and alpha-fetoprotein can increase the overall diagnosis rate of hepatocellular carcinoma to 88%. In addition, the DKK1 concentration in the patient's blood decreases rapidly after surgery, and serum DKK1 protein can also be used as an indicator for monitoring the efficacy of liver cancer and judging the prognosis.

The corresponding author of the paper, Researcher Qin Wenxin, is dedicated to the study of tumor microenvironment, tumor metastasis and early diagnosis of tumors. From the discovery that the secretory protein DKK1 in the tumor microenvironment can be used as a tumor serum protein marker to clinical trials, the entire research work has lasted for ten years. According to the publication requirements of The Lancet Oncology, the paper systematically reviews the originality, patent application and discovery history of the tumor serum protein marker DKK1. In addition, the paper also defines and discusses the standards that tumor serum protein markers with clinical application value should have. Recently, good news came from the United States Patent and Trademark Office. The applied international patent "Application of DKK1 in Cancer Diagnosis" has been authorized by the United States Patent, which provides intellectual property protection for the tumor serum protein marker DKK1 diagnostic products to occupy the international market. According to Shen Qiujin, the first author of the paper and a doctoral student, a serum DKK1 protein detection system with independent intellectual property rights has been initially developed, and further follow-up clinical trials are underway with the concerted efforts of relevant units. The clinical transformation of the tumor serum protein marker DKK1 still needs the joint promotion of relevant national departments, the Shanghai Municipal Government and enterprises to industrialize the tumor serum protein marker DKK1 and apply it in clinical practice as soon as possible to benefit the majority of cancer patients.

This research was jointly funded by the National Key Research and Development Program, the National 973 Program, and the National Natural Science Foundation of China.