Serum marker for liver cancer

Abstract

The invention belongs to the technical field of laboratory medicine, and discloses a liver cancer serum marker putrescine. The application value of metabolite putrescine in early diagnosis of liver cancer is investigated, and the result shows that in liver cancer patients, the expression of putrescine metabolism synthesis key enzyme ODC1 is remarkably up-regulated, the content of putrescine in serum specimens of clinical liver cancer patients is remarkably increased, and the proliferation capacity of liver cancer cells is remarkably inhibited by knocking down ODC1. The results indicate that the metabolite putrescine can be used for early diagnosis of liver cancer and has the potential of promoting clinical diagnosis and treatment.

Description

Technical Field

[0001] The invention belongs to the technical field of laboratory medicine, and in particular relates to a serum marker for liver cancer. Background Art

[0002] Primary liver cancer is the sixth most common malignant tumor in the world and the third leading cause of cancer-related deaths worldwide. Among them, hepatocellular carcinoma (HCC) (hereinafter referred to as liver cancer) clinically accounts for about 80% of primary liver cancer. At present, due to the lack of effective early detection methods, some patients have progressed to the late stage when liver cancer is diagnosed, thus delaying the best treatment time and leading to poor prognosis. Therefore, further exploration of prognostic biomarkers and promising therapeutic targets related to liver cancer progression and metastasis is of great clinical significance.

[0003] Alpha-fetoprotein (AFP), AFP-L3 and des-γ-carboxyprothrombin (DCP) are widely used as serological indicators for liver cancer screening due to their high expression in the serum of HCC patients. Currently, the most widely used serum marker for HCC in clinical practice is AFP, but serum AFP does not change significantly in nearly one-third of liver cancer patients.

[0004] However, DCP is often affected by many factors, which leads to its abnormal increase, thus interfering with the diagnosis of liver cancer. Therefore, finding a highly sensitive and specific serological marker for liver cancer is of great significance for the differential diagnosis of liver cancer and the judgment of disease progression.

[0005] Polyamines (PA), including putrescine, spermidine and spermine, are essential polycationic substances in living organisms. Polyamines carry multiple positive charges and have a high affinity for nucleic acids. They regulate DNA replication, gene transcription and cell division. Polyamine homeostasis is essential for maintaining normal cell growth and proliferation in the body. The first step in polyamine biosynthesis is the conversion of arginine to ornithine by arginine kinase 1 (ARG1), followed by ornithine decarboxylase (ODC1) converting ornithine to putrescine. Putrescine is then translated by spermidine synthase (SRM) and spermine synthase (SMS) to produce spermidine and spermine. Among them, ODC1 is the key enzyme in the putrescine synthesis process.

[0006] High levels of putrescine expression in tumors are associated with the occurrence and development of a variety of diseases. In tumor cells, polyamines (including putrescine) are widely involved in regulating intracellular redox balance as free radical scavengers. Highly expressed polyamines can regulate gene expression, evade immune detection, promote malignant proliferation, etc. However, there are few reports on the regulation of putrescine on liver cancer cells. Exploring the differences in the demand for putrescine between normal cells and tumor cells may provide new therapeutic means for finding targeted metabolic pathways in anti-tumor treatment. Summary of the invention

[0007] In view of this, the purpose of the present invention is to provide a serum marker for liver cancer. The present invention aims to solve the problems of low sensitivity, poor specificity and inaccurate detection results of existing serum markers for liver cancer.

[0008] To achieve the above object, the present invention provides a new use of putrescine.

[0009] The technical solution adopted by the present invention is: application of putrescine as a diagnostic marker for liver cancer.

[0010] Application as a serum marker for liver cancer.

[0011] Application as a marker in the preparation of detection products for diagnosing liver cancer.

[0012] Application as a marker in the preparation of detection products for liver cancer staging.

[0013] as serum markers.

[0014] The detection product is used for detecting serum.

[0015] The detection product is a diagnostic kit.

[0016] The present invention also provides a kit for diagnosing liver cancer or staging liver cancer, wherein the kit comprises a reagent for specifically detecting serum putrescine.

[0017] Beneficial effects of the present invention:

[0018] The present invention investigates the application value of the metabolite putrescine in the early diagnosis of liver cancer. The results show that in patients with liver cancer, the expression of ODC1, a key enzyme in the metabolism and synthesis of putrescine, is significantly upregulated, the content of putrescine in serum specimens of clinical liver cancer patients is significantly increased, and knocking down ODC1 significantly inhibits the proliferation of liver cancer cells. The above results suggest that the metabolite putrescine can be used for the early diagnosis of liver cancer and has the potential to be promoted to clinical diagnosis and treatment. Finally, the present invention provides a serum marker for liver cancer and a kit for diagnosing liver cancer.

[0019] Other advantages, objectives and features of the present invention will be described in the following description to some extent, and to some extent, will be obvious to those skilled in the art based on the following examination and study, or can be taught from the practice of the present invention. The objectives and other advantages of the present invention can be realized and obtained through the following description. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The expression of ODC1 in HCC tissues and corresponding non-cancerous liver tissues in the TCGA database;

[0021] Figure 2 Serum putrescine content in liver cancer patients and normal subjects;

[0022] Figure 3 Knocking down ODC1 inhibits the proliferation ability of liver cancer cells. DETAILED DESCRIPTION

[0023] In order to make the technical solutions, advantages and purposes of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the described embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work belong to the protection scope of this application.

[0024] The present invention provides a new use of putrescine:

[0025] Application as a diagnostic marker for liver cancer;

[0026] Application as a serum marker for liver cancer;

[0027] Application as a marker in the preparation of detection products for diagnosing liver cancer;

[0028] Application as a marker in the preparation of detection products for liver cancer staging.

[0029] The present invention also provides a kit for diagnosing liver cancer or staging liver cancer, wherein the kit comprises a reagent for specifically detecting serum putrescine.

[0030] Data analysis and experimental analysis

[0031] 1. Increased expression of ODC1 in hepatocellular carcinoma

[0032] Based on the data from The Cancer Genome Atlas (TCGA), the expression of ODC1 in HCC was analyzed. Figure 1As shown, ODC1 expression was upregulated in HCC tissues compared with adjacent adjacent tissues.

[0033] 2. Detection of the metabolite putrescine in the serum of clinical liver cancer patients

[0034] The serum levels of putrescine metabolite were collected and tested in patients with clinical liver cancer (n=54) and healthy subjects (n=45). Figure 2 As shown, the level of putrescine in the serum of liver cancer patients was significantly increased compared with that in normal human serum.

[0035] 3. Detection of the effect of metabolite putrescine on the proliferation ability of liver cancer cells

[0036] In order to verify the physiological function of the metabolite putrescine, the key enzyme ODC1 for putrescine synthesis was knocked down in PLC / PRF / 5 and MHCC-97H cells in this example. The EDU experiment confirmed that the proliferation ability of liver cancer cells in the shODC1 treatment group was significantly weakened compared with the shGFP group. Figure 3 .

[0037] The present invention also provides a new use of ornithine decarboxylase ODC1:

[0038] Application as a diagnostic marker for liver cancer;

[0039] Application as a serum marker for liver cancer;

[0040] Application as a marker in the preparation of detection products for diagnosing liver cancer;

[0041] Application as a marker in the preparation of detection products for liver cancer staging.

[0042] The present invention also provides a kit for diagnosing liver cancer or staging liver cancer, wherein the kit comprises a reagent for specifically detecting serum ornithine decarboxylase ODC1, wherein the ornithine decarboxylase ODC1 is a key enzyme for putrescine synthesis.

[0043] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the present invention. Anyone familiar with the technology may modify or change the above embodiments without violating the spirit and scope of the present invention. Therefore, all equivalent modifications or changes made by those with ordinary knowledge in the technical field without departing from the spirit and technical ideas disclosed by the present invention should still be covered by the claims of the present invention.

Claims

1. The application of putrescine as a marker in the preparation of detection products for specific identification of liver cancer.

2. The use according to claim 1, characterized in that: Putrescine as a serum marker.

3. The use according to claim 1, characterized in that: The detection product is used for detecting serum.

4. The use according to claim 1, characterized in that: The detection product is a diagnostic kit.

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