Search

KR-102962374-B1 - Composition for diagnosing pancreatic cancer

KR102962374B1KR 102962374 B1KR102962374 B1KR 102962374B1KR-102962374-B1

Abstract

The present invention relates to a composition, a kit, and a method for providing information for diagnosis that can diagnose pancreatic cancer and distinguish it from other pancreatic diseases or other types of cancer.

Inventors

  • 이형근
  • 이동기
  • 김소영
  • 장성일

Assignees

  • (주)아큐레시스바이오

Dates

Publication Date
20260512
Application Date
20220516

Claims (20)

  1. A biomarker composition for the diagnosis of pancreatic cancer comprising the LILRB5 (leukocyte immunoglobulin like receptor B5) protein or a gene encoding it.
  2. In paragraph 1, The above biomarker composition further comprises a CAMP (cathelicidin antimicrobial peptide) protein or a gene encoding the same.
  3. A composition for diagnosing pancreatic cancer comprising, as an active ingredient, a preparation for measuring the expression level of the LILRB5 (leukocyte immunoglobulin like receptor B5) protein or the gene encoding it.
  4. In paragraph 3, The above diagnostic composition further comprises a preparation for measuring the expression level of a CAMP (cathelicidin antimicrobial peptide) protein or a gene encoding it.
  5. In paragraph 3, A diagnostic composition comprising one or more selected from the group consisting of antibodies, oligopeptides, ligands, PNA (peptide nucleic acid), and aptamers that specifically bind to the protein, for measuring the expression level of the protein.
  6. In paragraph 3, A diagnostic composition comprising one or more selected from the group consisting of primers, probes, and antisense nucleotides that specifically bind to the gene, for measuring the expression level of the gene.
  7. A diagnostic kit for pancreatic cancer comprising a diagnostic composition according to any one of paragraphs 3 to 6.
  8. The method includes the step of measuring the expression level of the LILRB5 (leukocyte immunoglobulin like receptor B5) protein or the gene encoding it in a biological sample isolated from a target individual, and A method for providing information for the diagnosis of pancreatic cancer, wherein the expression level of the LILRB5 protein or the gene encoding it, measured for a biological sample of the above-mentioned target individual, is higher than that of a control group to determine pancreatic cancer.
  9. In paragraph 8, The above information providing method further comprises the step of measuring the expression level of a CAMP (cathelicidin antimicrobial peptide) protein or a gene encoding it in a biological sample isolated from the above-mentioned target individual.
  10. In paragraph 8, A method for providing information, wherein a preparation for measuring the expression level of the above protein comprises one or more selected from the group consisting of antibodies, oligopeptides, ligands, PNA (peptide nucleic acid), and aptamers that specifically bind to the above protein.
  11. In paragraph 8, A method for providing information, wherein the measurement of the expression level of the above protein is performed by protein chip analysis, immunoassay, ligand binding assay, MALDI-TOF (Matrix Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry) analysis, SELDI-TOF (Surface Enhanced Laser Desorption/Ionization Time of Flight Mass Spectrometry) analysis, radioimmunoassay, radioimmunodiffusion, Ouchteroni immunodiffusion, Rocket immunoelectrophoresis, tissue immunostaining, complement fixation assay, two-dimensional electrophoresis analysis, liquid chromatography-mass spectrometry (LC-MS), LC-MS/MS (liquid chromatography-mass spectrometry/mass spectrometry), multiple reaction monitoring (MRM), Western blotting, or ELISA (enzyme-linked immunosorbent assay).
  12. In paragraph 8, A method for providing information, wherein a preparation for measuring the expression level of the above gene comprises one or more selected from the group consisting of primers, probes, and antisense nucleotides that specifically bind to the above gene.
  13. In paragraph 8, A method for providing information, wherein the measurement of the expression level of the above gene is performed by reverse transcription polymerase chain reaction (RT-PCR), competitive reverse transcription polymerase chain reaction (Competitive RT-PCR), real-time reverse transcription polymerase chain reaction (Real-time RT-PCR), RNase protection assay (RPA), Northern blotting, or a DNA chip.
  14. delete
  15. A biomarker composition for distinguishing pancreatic cancer from pancreatic inflammation or pancreatic benign tumor, comprising at least one protein among LILRB5 (leukocyte immunoglobulin like receptor B5) and CAMP (cathelicidin antimicrobial peptide) or a gene encoding the same.
  16. A diagnostic composition for distinguishing pancreatic cancer from pancreatic inflammation or pancreatic benign tumor, comprising as an active ingredient a preparation for measuring the expression level of at least one protein among LILRB5 (leukocyte immunoglobulin like receptor B5) and CAMP (cathelicidin antimicrobial peptide) or a gene encoding it.
  17. A diagnostic kit for distinguishing pancreatic cancer from pancreatic inflammation or pancreatic benign tumors, comprising the diagnostic composition of claim 16.
  18. The method comprises the step of measuring the expression level of at least one protein among LILRB5 (leukocyte immunoglobulin like receptor B5) and CAMP (cathelicidin antimicrobial peptide) or a gene encoding the same in a biological sample isolated from a target individual having developed a lesion or tumor in the pancreas, A method for providing information to distinguish pancreatic cancer from pancreatic inflammation or a benign pancreatic tumor, wherein the expression level of the LILRB5 protein or the gene encoding it measured in a biological sample of the above-mentioned target individual is higher than that of a control group, or the expression level of the CAMP protein or the gene encoding it measured is lower than that of a control group, and the pancreatic lesion or tumor is predicted to be pancreatic cancer.
  19. delete
  20. delete

Description

Composition for diagnosing pancreatic cancer The present invention relates to a composition, a kit, and a method for providing information for diagnosis of pancreatic cancer. Among the major diseases affecting modern people, research on cancer treatment and diagnosis methods is being conducted relatively actively, focusing on cancers with high incidence rates such as lung, liver, and stomach cancers. However, research on cancers with low incidence rates, such as esophageal, colorectal, and pancreatic cancers, is relatively lacking. In particular, pancreatic cancer often presents with few symptoms in the early stages, and symptoms such as pain and weight loss typically appear only after metastasis has already occurred. Since this results in a lower cure rate, regular checkups are crucial. Clinical symptoms mostly develop gradually, and patients are prone to weakness; loss of appetite and weight loss are the most common symptoms. Pancreatic cancer is a fatal disease with a 5-year survival rate of 1-4% and a median survival of 5 months, exhibiting the worst prognosis among all cancers in the human body. Furthermore, because 80-90% of patients are diagnosed at a stage where curative resection—which offers the possibility of a cure—is impossible, the prognosis is poor and treatment relies primarily on chemotherapy. Consequently, the development of early diagnostic methods is more urgently needed for pancreatic cancer than for any other human cancer. The therapeutic efficacy of several anticancer drugs known to be effective against pancreatic cancer to date, including 5-fluorouracil, gemcitabine, and tarceva, is extremely poor, with a response rate of only around 15%. This suggests that the development of more effective early diagnostic and therapeutic methods is urgently required to improve the prognosis of pancreatic cancer patients. Appropriate diagnosis and treatment of pancreatic cancer precursor lesions, which are the stage before progression to fatal pancreatic cancer, are crucial for improving treatment outcomes. The diagnosis of pancreatic cancer or precancerous lesions is currently performed using blood tests (CA19-9), X-ray contrast studies of the stomach and duodenum, transcutaneous and transhepatic cholangiography, and retrograde endoscopic cholangiography. While these methods have been effective in detecting disease lesions, ultrasound and computed tomography (CT) are currently the most widely used methods. Relatively accurate results can also be obtained by performing more precise biopsies. However, the aforementioned diagnostic methods are often inconvenient to perform, such as having lower accuracy or causing pain to the patient, leading patients to avoid them. Therefore, there has been a demand for the development of a diagnostic method that can diagnose pancreatic cancer or precancerous lesions simply and rapidly. Korean Patent No. 10-0819122 and Korean Published Patent No. 2012-0082372 disclose technology using various pancreatic cancer markers including matrilin, transthyretin, and stratifin, but since there are significant differences in diagnostic efficiency and accuracy among the markers, there is a need to discover markers with superior efficacy and develop diagnostic methods using them. Figure 1 shows the results of analyzing the mRNA expression levels of LILRB5 by qPCR in samples from the pancreatic cancer patient group, normal population group, high-risk group (pancreatic cyst, chronic pancreatitis, etc.), and benign pancreatic disease patient group (acute pancreatitis, pancreatic lipoma) in Experimental Example 2. Figure 2 shows the ROC curve for diagnosing pancreatic cancer based on the results of analyzing the mRNA expression levels of LILRB5 in samples from the pancreatic cancer patient group and the pancreatic cyst patient group in Experimental Example 2. Figure 3 shows the results of analyzing the mRNA expression levels of CAMP in samples from the pancreatic cancer patient group, the acute pancreatitis patient group, and the pancreatic benign tumor patient group in Experimental Example 2 by confirming them with qPCR. Figure 4 shows the ROC curve for diagnosing pancreatic cancer based on the results of analyzing the mRNA expression levels of CAMP in samples from the pancreatic cancer patient group and the acute pancreatitis patient group in Experimental Example 2. The present invention will be explained in detail below through the following examples. However, the following examples are merely illustrative of the present invention, and the scope of the present invention is not limited by the following examples. Examples [Experimental Example 1] Screening of Pancreatic Cancer Diagnostic Markers In cases of chronic or acute pancreatic disease or pancreatic tumors, the process of differentiating them from pancreatic cancer is extremely complex, and the examination process is invasive. Therefore, in the following experiments, non-invasive marker discovery was performed to differentiate