CN115449551A - Application of TFF1 and TFF3 in early diagnosis of lung cancer bone metastasis - Google Patents
Application of TFF1 and TFF3 in early diagnosis of lung cancer bone metastasis Download PDFInfo
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Abstract
The invention belongs to the technical field of biological medicines, discloses application of TFF1 and TFF3 in early diagnosis of lung cancer bone metastasis, and particularly discloses application of a substance for detecting biomarkers in preparation of a product for diagnosing or early screening lung cancer bone metastasis; the biomarker comprises TFF1 and/or TFF3. The invention discloses the relation between the expression of secreted proteins TFF1 and TFF3 and the specific lung cancer bone metastasis for the first time, verifies that the secreted proteins TFF1 and TFF3 are specifically and highly expressed in a serum sample of a patient with the lung cancer bone metastasis and lung cancer bone metastasis cells, and prompts that the secreted proteins TFF1 and TFF3 can be used as a novel lung cancer bone metastasis diagnosis marker, so that a lung cancer patient with bone metastasis can be obviously distinguished from lung cancer patients and healthy people with other organ metastasis.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to application of TFF1 and TFF3 in early diagnosis of bone metastasis of lung cancer.
Background
The morbidity and mortality of lung cancer is high in leaderboard among all tumors worldwide. For a long time, the survival rate of lung cancer patients is extremely low, and particularly, the five-year survival rate of the lung cancer patients in middle and advanced stages is only 9 percent and 1 percent respectively. In actual clinical diagnosis, 60-80% of patients are in advanced stage at the early stage of diagnosis, and the prognosis is poor. Metastasis is responsible for death in more than 90% of patients with tumors, with bone being the most common and most symptomatic metastatic organ in advanced lung cancer. The low early diagnosis rate is considered to be the main cause of high mortality and poor prognosis in patients with bone metastases of lung cancer.
The early stage of bone metastasis is usually free of any symptoms, and the symptoms are related to the position and the number of tumor metastasis. When patients present with typical symptoms of bone metastasis such as bone pain, pathological fractures, etc. to seek medical attention, a large metastasis has generally developed. In clinical practice, bone imaging is often used to determine whether a tumor patient has bone metastasis, such as: radionuclide bone scanning, PET-CT, MRI and the like, but the methods have the defects of high cost, untimely diagnosis and the like, and have certain limitations on sensitivity, specificity and operability.
In recent years, there has been some progress in the study of biomarkers for the diagnosis of bone metastasis. Researchers found that serum levels of ProGRP were significantly elevated in patients with bone metastases relative to prostate cancer patients without bone metastases. Through prospective studies, researchers found that the presence of osteocalcin-positive circulating tumor cells meant that patients were more susceptible to bone metastasis. In patients with advanced lung cancer, the expression levels of proteins such as CXCR4, BSP, OPN, and BMP4 in tumor cells are positively correlated with the risk of bone metastasis. However, the above studies are currently in preclinical research stage, and no specific tumor markers of bone metastasis are introduced clinically, especially for lung cancer, so that it is very urgent to explore the molecular mechanism of bone metastasis of lung cancer, and find new, highly sensitive and easily detectable early diagnosis markers of bone metastasis.
Disclosure of Invention
The first aspect of the present invention aims at providing the application of the material for detecting the biomarker in the preparation of products for diagnosing or early screening bone metastasis of lung cancer.
The second aspect of the invention aims to provide application of TFF1 and/or TFF3 as a biomarker in preparation of a product for early diagnosis of bone metastasis of lung cancer.
The third aspect of the invention aims to provide the application of TFF1 and/or TFF3 inhibitory agents in preparing medicaments for preventing, inhibiting and/or treating lung cancer bone metastasis.
The fourth aspect of the invention aims to provide the application of TFF1 and/or TFF3 as a target point in screening drugs for treating or preventing bone metastasis of lung cancer.
In a fifth aspect, the present invention is directed to a marker combination.
The sixth aspect of the invention aims to provide a product.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
in a first aspect of the present invention, there is provided a use of a substance for detecting a biomarker for preparing a product for diagnosing or early screening bone metastasis of lung cancer; the biomarker comprises TFF1 and/or TFF3.
Preferably, the substance comprises a substance that quantitatively detects a biomarker.
Preferably, the biomarker detection substance comprises a biomarker detection substance at the gene level and/or protein level.
Preferably, the means for detecting a biomarker is a means for use in one or more detection techniques or methods selected from the group consisting of: enzyme-linked immunosorbent assay, immunofluorescence assay, radioimmunoassay, co-immunoprecipitation, immunoblotting, high performance liquid chromatography, capillary gel electrophoresis, near infrared spectroscopy, mass spectrometry, immunochemiluminescence, colloidal gold immunoassay, fluorescence immunochromatography, surface plasmon resonance, immuno-PCR or biotin-avidin.
Preferably, the biomarker-detecting substance is selected from the group consisting of: a substance specific to TFF1 and/or TFF3, a probe specific to TFF1 and/or TFF3, a gene chip, a PCR primer, and the like.
Preferably, the substance specific to TFF1 and/or TFF3 is any one of (b 1) to (b 3):
(b1) An antibody that specifically binds to TFF1 and/or TFF 3;
(b2) A ligand protein or polypeptide that specifically binds TFF1 and/or TFF 3;
(b3) A non-proteinaceous compound that specifically recognizes TFF1 and/or TFF3.
Preferably, the antibody comprises at least one of polyclonal antibody, monoclonal antibody, single-chain antibody, functional antibody fragment, antibody Fab region, nanobody, chimeric antibody and multispecific antibody.
Preferably, the product comprises at least one of a reagent, a kit, a strip, a chip.
Preferably, the sample of the subject of the product may be selected from a body fluid sample, a tumor sample and a cell sample isolated from the subject.
Preferably, the bodily fluid includes, but is not limited to, blood, plasma, serum, lymph, cerebrospinal fluid, synovial fluid, urine, saliva, mucus, and the like; the form of the tumor sample includes but is not limited to the form of living tissue, paraffin-embedded tissue, frozen tissue and the like; the cell sample may be selected from cells that can be isolated from a subject, such as peripheral blood mononuclear cells, T lymphocytes, B lymphocytes, circulating tumor cells, and the like.
Preferably, when the TFF1 and/or TFF3 of the test object is significantly increased relative to the reference level, the bone metastasis of the lung cancer is diagnosed; the reference level is the level of a subject of the same age group who does not have a bone metastasis from lung cancer.
Preferably, the subjects of the same age group are healthy persons and lung cancer patients without bone metastases.
The term "bone metastasis free" in the medical field means that bone metastasis does not occur, and generally, a collected tumor sample is analyzed and classified as a bone metastasis free tumor sample if the tumor sample does not have bone metastasis, and those skilled in the art should understand that the bone metastasis free tumor sample may be a tumor sample in which no metastasis occurs and may also be a tumor sample in which other non-bone metastasis (such as liver, brain, lung) occurs.
Preferably, the lung cancer comprises non-small cell lung cancer and small cell lung cancer.
Preferably, the non-small cell lung cancer comprises squamous cell carcinoma (squamous carcinoma), adenocarcinoma, large cell carcinoma.
Preferably, said TFF1 and/or TFF3 is up-regulated in patients with bone metastases from lung cancer.
In a second aspect of the invention, the application of TFF1 and/or TFF3 as a biomarker in the preparation of a product for early diagnosis of bone metastasis of lung cancer is provided.
Preferably, the product comprises at least one of a reagent, a kit, a strip, a chip.
In a third aspect of the invention, there is provided the use of an inhibitory agent of TFF1 and/or TFF3 in the manufacture of a medicament for the prevention, inhibition and/or prevention of bone metastasis from lung cancer.
Preferably, said inhibitory agent of TFF1 and/or TFF3 comprises a substance capable of inhibiting the expression of the TFF1 and/or TFF3 gene, in whole or in part, and/or a substance inhibiting the efficiency of the TFF1 and/or TFF3 protein.
Preferably, the inhibitory agent of TFF1 and/or TFF3 is selected from the group consisting of: proteins, oligonucleotides, oligonucleotide expression vectors, small molecule compounds.
Preferably, the expression vector comprises a eukaryotic cell expression vector, which comprises a plasmid expression vector or a viral expression vector.
In a fourth aspect of the present invention, the use of TFF1 and/or TFF3 as a target for screening a drug for treating or preventing bone metastasis from lung cancer is provided.
In a fifth aspect of the invention, there is provided a marker combination comprising TFF1 and TFF3.
Preferably, the marker combination consists of TFF1 and TFF3.
In a sixth aspect of the invention, there is provided a product comprising a substance which detects the marker combination of the fifth aspect of the invention.
The invention has the beneficial effects that:
the invention discloses the relation between the expression of secreted proteins TFF1 and TFF3 and the specific lung cancer bone metastasis for the first time, verifies that the secreted proteins TFF1 and TFF3 are specifically and highly expressed in a serum sample of a patient with the lung cancer bone metastasis and lung cancer bone metastasis cells, and prompts that the secreted proteins TFF1 and TFF3 can be used as a novel lung cancer bone metastasis diagnosis marker, so that a lung cancer patient with bone metastasis can be obviously distinguished from lung cancer patients and healthy people with other organ metastasis.
In clinical application, ELISA test can be used to detect TFF1 and TFF3 levels of patient blood samples, so as to judge the risk of bone metastasis of patients and implement early intervention treatment. Compared with the traditional bone metastasis diagnosis method such as tissue biopsy or imaging screening, the ELISA detection finds that the expression levels of TFF1 and TFF3 in the serum of a lung cancer bone patient are obviously increased, and prompts that the TFF expression level is obviously increased to indicate the possibility of bone metastasis of the patient, so that the related treatment is carried out more timely, and the better prognosis is brought to the patient; the operation is more convenient and feasible, the result is more sensitive, and the experiment cost is lower; from the patient's perspective, noninvasive detection of serum ELISA would impose far less psychological and economic burden on the patient.
Drawings
FIG. 1 shows the expression of TFF1 and TFF3 in the serum of lung cancer bone metastasis cells and patients; wherein, A is the expression condition of TFF1 and TFF3 in lung cancer bone metastasis cells, B is the expression condition of TFF1 in the serum of a patient with lung cancer bone metastasis, and C is the expression condition of TFF3 in the serum of the patient with lung cancer bone metastasis; d is a ROC curve of TFF1 for diagnosing bone metastasis of lung cancer, E is a ROC curve of TFF3 for diagnosing bone metastasis of lung cancer, and F is a ROC curve of TFF1 and TFF3 combined for diagnosing bone metastasis of lung cancer.
FIG. 2 is a graph showing the effect of TFF1 and TFF3 expression on bone metastasis of lung cancer in vivo in mice.
Detailed Description
The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the embodiments of the present application, and it is obvious that the described embodiments are only a part of the embodiments of the present application, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.
Reagents, methods and apparatus used in the present invention are conventional in the art unless otherwise indicated. Unless otherwise indicated, reagents and materials used in the following examples are commercially available. The experimental method not specified for the specific conditions is usually carried out under the conventional conditions or the conditions recommended by the manufacturer.
Example 1 expression of TFF1 and TFF3 in the serum of bone metastases from lung cancer and patients with bone metastases from lung cancer
The inventor group extracts PC9 bone metastasis (PC 9-BM) cells and PC9 lung metastasis (PC 9-LM) cells through in vivo screening of mice, finds that DKK3 in the PC9-BM cells is remarkably high-expressed, prompts that the expression of secretory protein DKK3 is related to lung cancer bone metastasis, and can be used as a blood molecular diagnosis marker for early bone metastasis of lung cancer. The inventor utilizes an enzyme-linked immunosorbent assay (ELISA) to detect the expression conditions of TFF1 and TFF3 in cell supernatants of lung cancer specific organ metastasis subcellular strains and in serum of lung cancer bone metastasis patients, verifies the specific secretion conditions of TFF1 and TFF3 in the serum of the bone metastasis cells and the lung cancer bone metastasis patients, and concretely comprises the following steps:
1. collecting cell supernatant/extracting serum from patient
Collecting fine particlesCell supernatant: at 2X 10 6 Inoculating PC9 parent cell (PC 9-PR), PC9-BM cell and PC9-LM cell in 100X 20mm culture dish; 37 ℃ C. 5% CO 2 Culturing for 24 hours, removing the culture medium, washing twice by using PBS, and removing the PBS; the culture was continued by adding 8mL of serum-free medium (Opti-MEM, gibco, catalog: # 31985070); after 48 hours, the cell supernatant was collected and filtered using a 0.45 μm filter to remove cell debris from the cell supernatant; the cell filtrate was collected and immediately subjected to subsequent experiments or stored at-40 ℃ until use.
Extraction of patient serum (serum was isolated from freshly collected whole blood): collecting whole blood of 20 healthy people, 33 early stage non-metastatic patients of lung cancer, and 45 patients with bone metastasis of lung cancer (from tumor control center of Zhongshan university) in anticoagulation tube (containing EDTA), and standing overnight at 4 deg.C; layering is visible after standing, the lower layer is blood plasma, and the upper layer is blood serum; sucking the upper clear yellow serum layer into a centrifuge tube, and centrifuging for 30 minutes at 4 ℃ and 2500 rpm; discarding the precipitate, sucking the upper layer serum component to obtain patient serum, and performing subsequent experiment or storing at-80 deg.C.
ELISA detection of expression levels of TFF1 and TFF3 in cell supernatants and serum samples
The expression level of TFF1 and TFF3 in cell supernatant and serum samples was determined by Duoset ELISA kit (R & D, catalog: # DY5237 and # DY 4407) from R & D company as follows:
(1) After the capture antibodies (R & D, PART: #843815, # 843133) were diluted to working concentration (2 mg/mL) using PBS solution, 100. Mu.L per well were added to ELISA 96-well plates and incubated overnight at room temperature (20 to 30 ℃);
(2) Discarding the capture antibody in the ELISA 96 holes, washing each hole for 3 times by using 400 mu L of ELISA wash buffer, after the last washing, reversely covering the ELISA 96 hole plate on absorbent paper, and slightly beating the plate to completely remove the residual ELISA wash buffer in the holes;
(3) Adding 300mL Reagent into each hole, incubating for 1 hour at room temperature, and sealing;
(4) Discard the Reagent Diluent from the wells, wash 3 times with 400 μ L ELISA wash buffer per well; after the last washing, the ELISA 96 pore plate is reversely buckled on absorbent paper, and the plate is lightly patted to completely remove residual ELISA wash buffer in the pore;
(5) Diluting a TFF1 protein standard (R & D, PART: # 843817) to 15.6pg/mL, 31.3pg/mL, 62.5pg/mL, 125pg/mL, 250pg/mL, 500pg/mL, 1000pg/mL, diluting a TFF3 protein standard (R & D, PART: # 843135) to 7.8pg/mL, 15.6pg/mL, 31.3pg/mL, 62.5pg/mL, 125pg/mL, 250pg/mL, 500pg/mL, adding the diluted protein standard and a sample to be tested to a 96-well plate, adding 100. Mu.L of pg/well, and incubating at room temperature for 2 hours according to the instructions;
(6) The wells were discarded and each well was washed 3 times with 400 μ L ELISA wash buffer; after the last washing, reversely covering the ELISA 96 pore plate on absorbent paper, and slightly patting the plate until completely removing residual ELISA wash buffers in the pores;
(7) mu.L of TFF1 detection antibody (R & D, PART: #843816, concentration 100 ng/mL) or TFF3 detection antibody (R & D, PART: #843134, concentration 100 ng/mL) was added to each well and incubated at room temperature for 2 hours;
(8) Discarding the liquid in the wells, washing 3 times with 400 μ L ELISA wash buffer per well; after the last washing, reversely covering the ELISA 96 pore plate on absorbent paper, and slightly patting the plate until completely removing residual ELISA wash buffers in the pores;
(9) Add 100. Mu.L of Streptavidin-HRP (200X) to each well and incubate for 20 min at room temperature in the dark;
(10) Discarding the liquid in the wells, washing 3 times with 400 μ L ELISA wash buffer per well; after the last washing, reversely covering the ELISA 96 pore plate on absorbent paper, and slightly patting the plate until completely removing residual ELISA wash buffers in the pores;
(11) Adding 100 mu L of chromogenic solution (Substrate solution) into each hole for developing, and incubating for 20 minutes in a dark room temperature after adding the chromogenic solution;
(12) Adding 50 mu L of chromogenic Stop solution (Stop solution) into each hole to Stop reaction, and tapping the hole plate after adding the Stop solution to completely mix the solution;
(13) Immediately detecting absorbance value at 450nm with multifunctional microplate reader after termination, according to OD of standard 450nm Value calculating regression curve, and calculating egg of sample to be testedWhite concentration.
The results are shown in fig. 1, and the expression of TFF1 and TFF3 is specifically up-regulated in the lung cancer bone metastasis cells (a in fig. 1), and has statistical significance (p < 0.0001). In the serum samples of patients with lung cancer bone metastasis, both TFF1 and TFF3 showed specific up-regulation in the serum samples of patients with lung cancer bone metastasis (B-C in FIG. 1), and had statistical significance (p < 0.0001).
In order to further score the value of secreted proteins TFF1 and TFF3 in early diagnosis of lung cancer bone metastasis, the inventor constructs an ROC curve for the secreted proteins TFF1 and TFF3 to predict the lung cancer bone metastasis of a lung cancer patient by referring to the clinical pathological diagnosis result. As a result, as shown in D in FIG. 1, the secreted protein TFF1 had an AUC in distinguishing between bone metastasis and non-bone metastasis (including healthy and early non-metastasis) of 0.8897, 95% CI (0.8247 to 0.9548), an AUC in distinguishing between healthy and early non-bone metastasis of 0.6258, 95% CI (0.4636 to 0.7879), an AUC in distinguishing between early non-bone metastasis and bone metastasis of 0.9017, and 95% CI (0.8374 to 0.966); as shown in E in fig. 1, the AUC of the secreted protein TFF3 in distinguishing between bone metastasis and non-bone metastasis (including healthy and early non-metastasis) was 0.9825, 95% ci (0.8247-0.9548), the AUC in distinguishing between healthy humans and early non-bone metastasis was 0.534, 95% ci (0.3751-0.6929), the AUC in distinguishing between early non-bone metastasis and bone metastasis was 0.9728, 95% ci (0.9373-1.008); when the secreted proteins TFF1 and TFF3 were used in combination, the AUC distinguishing early non-bone metastases from bone metastases lung cancer patients was 0.987, 95% CI (0.966-1.000), the AUC distinguishing non-bone metastases (including healthy and early non-metastases) from bone metastases was 0.995, 95% CI (0.986-1.000) (FIG. 1F), and the above results indicate that the secreted proteins TFF1, TFF3 have better accuracy specificity in predicting early diagnosis in lung cancer patients.
Example 2 in vivo experiments in mice to examine the influence of TFF1 and TFF3 expression on bone metastasis of lung cancer
Establishment of TFF1 and TFF3 Stable and high-expression Lung cancer cell lines (PC 9TFF 1 cells and PC9TFF3 cells)
Generally, a lentivirus vector is used for preparing virus solution (a cell culture solution containing virus plasmid particles, referred to as virus solution for short), the transfection method comprises lipofection and calcium phosphate transfection, and the experimental method of the virus transfection is described by taking the lipofection as an example.
Preparation before transfection: the number of cells is about 2.0 to 3.0X 10 6 The/8 mLCD human embryonic kidney cells (293 FT cells) were plated into 100X 20mm cell culture dishes; observing the cell state under a microscope after 24 hours to ensure that the cell state is good, and preparing a transfection system: liquid A and liquid B, wherein the liquid A: 6 μ g of psPAX2 (Addgene, catalog: # 12260), 4 μ g of pMD2.G (Addgene, catalog: # 12269), 10 μ g of TFF1 high expression plasmid (Veitl Biotech Co., ltd., catalog: # CH 892913) or TFF3 high expression plasmid (Veitl Biotech Co., ltd., catalog: # CH 801849), 15 μ L of p3000 (Thermo, catalog: # L3000-015), and 500 μ L of Op-MEM (Gibco, catalog: # 31985070), B fluid: 500 μ L of Opti-MEM and 20 μ L of lipofectamine 3000 (Thermo, catalog: # L3000-015);
transfection: mixing the solution A and the solution B gently, standing at room temperature for 20 minutes, slowly and uniformly dripping the mixed solution into 293FT cells with good growth, transfecting for 4-6 hours, and observing the cell state;
collecting virus liquid: after 24 hours of transfection, a 10mL syringe is used for collecting virus liquid, a filter with the pore diameter of 0.45 mu m is used for filtering to remove cell debris, and the filtrate is collected, namely the virus liquid; meanwhile, adding a fresh culture medium into 293FT cells for continuous culture;
preparation of infected cells: the number of cells on the day of infection was about 1.5X 10 5 After digesting and re-suspending cells to be infected (PC 9 cells) of the 4mLCD, the cells are uniformly paved to 25cm 2 In a cell culture flask;
infecting the cells: adding 40mg/mL Polybrene (Polybrene) solution into the collected virus solution according to the volume ratio of 1.
Screening positive cells: three days after continuous infection, puromycin solution (10 mg/mL) was added to the culture medium at a volume ratio of 1; adding a culture medium containing Puromycin into infected cells to screen positive cells, screening for 7 days, observing the cell state and death condition every day, changing liquid in time, collecting the positive cells after the positive cells grow stably, extracting cell RNA by using a Trizol method, extracting cell protein by using SDS protein lysate (Biyunyan, catalog: # P0013G), and performing stable over-expression cell strain efficiency verification through qRT-PCR and Western blot experiments; expanding or freezing the cells after successful verification to obtain PC9TFF 1 cells and PC9TFF3 cells;
2. in-vivo experiment of mice detects influence of TFF1 and TFF3 on bone metastasis of lung cancer
Preparation of tumor cell suspension: PC9TFF 1 cells and PC9TFF3 cells were digested and counted, and PC9 Vector cells were used as a control group, and the cells were resuspended in PBS solution to a cell concentration of 5X 10 5 /100μL；
Selecting 6-8 weeks old balb/c-nu/nu mice, 10 mice in total, and dividing the mice into 3 groups, a control group (injecting PC9 Vector cells), a PC9TFF 1 group (injecting PC9TFF 1 cells) and a PC9TFF3 group (injecting PC9TFF3 cells) at random on average; each mouse was intraperitoneally injected with 100 μ L of 4% chloral hydrate to anesthetize the mice; inoculating tumor cell suspension to the left ventricle of the mouse, injecting 100uL into each mouse, paying attention to the fact that the injector does not enter air bubbles, and when the positioning is accurate, blood in the injector is ejected; mice were routinely cultured after injection and tumor metastasis was observed continuously for 2-6 weeks using live imaging of the mice.
As shown in fig. 2, 4 weeks after tumor cell inoculation, the bone metastasis ability of the lung cancer cell lines of the PC9TFF 1 group and the PC9TFF3 group was significantly enhanced compared to the PC9 Vector group, i.e., the bone metastasis ability of the lung cancer cell lines with TFF1 and TFF3 stably and highly expressed was significantly enhanced, indicating that TFF1 and TFF3 play an important role in the bone metastasis process of lung cancer.
The embodiments of the present invention have been described in detail with reference to the drawings, but the present invention is not limited to the embodiments, and various changes can be made within the knowledge of those skilled in the art without departing from the gist of the present invention. Furthermore, the embodiments of the present invention and features of the embodiments may be combined with each other without conflict.
Claims (10)
1. Use of a substance for detecting biomarkers comprising TFF1 and/or TFF3 in the manufacture of a product for diagnosis or early screening of bone metastasis of lung cancer.
2. The use of claim 1, wherein the substance comprises a substance that quantitatively detects a biomarker.
3. Use according to claim 2, wherein the biomarker detection means comprises means for detecting the biomarker at the gene level and/or protein level.
4. Use according to claim 3, wherein the substance for detecting a biomarker is a substance used in one or more detection techniques or methods selected from the group consisting of: enzyme-linked immunosorbent assay, immunofluorescence assay, radioimmunoassay, co-immunoprecipitation, immunoblotting, high performance liquid chromatography, capillary gel electrophoresis, near infrared spectroscopy, mass spectrometry, immunochemiluminescence, colloidal gold immunoassay, fluorescence immunochromatography, surface plasmon resonance, immuno-PCR or biotin-avidin.
5. The use according to any one of claims 1 to 4, wherein the product comprises at least one of a reagent, a kit, a strip, a chip.
And 6, application of TFF1 and/or TFF3 as a biomarker in preparation of a product for early diagnosis of bone metastasis of lung cancer.
The application of the inhibitory reagent of TFF1 and/or TFF3 in preparing the medicine for preventing, inhibiting and/or treating the bone metastasis of the lung cancer, preferably, the inhibitory reagent of TFF1 and/or TFF3 comprises a substance capable of completely or partially inhibiting the expression of TFF1 and/or TFF3 genes and/or a substance inhibiting the TFF1 and/or TFF3 proteins from playing effects.
The application of TFF1 and/or TFF3 as a target point in screening a medicament for treating or preventing bone metastasis of lung cancer.
9. A marker combination comprising TFF1 and TFF3.
10. A product comprising a substance that detects the marker combination of claim 9.
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