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KR-20260064263-A - Biomarker composition for early hepatocellular carcinoma diagnosis comprising PRL, EIF1AY and PNPT1

KR20260064263AKR 20260064263 AKR20260064263 AKR 20260064263AKR-20260064263-A

Abstract

The present invention relates to biomarkers for the diagnosis of early liver cancer, namely PRL (Prolactin), EIF1AY (Eukaryotic translation initiation factor 1A, Y-linked), and PNPT1 (Polyribonucleotide nucleotidyltransferase 1). It was confirmed that the biomarkers PRL, EIF1AY, and PNPT1 for the diagnosis of early liver cancer according to the present invention are significantly overexpressed in the blood of patients with early liver cancer and can clearly distinguish early liver cancer from other liver diseases (hepatitis, cirrhosis). Furthermore, it was confirmed that when the discovered biomarkers PRL, EIF1AY, and PNPT1 are combined, the sensitivity, specificity, and diagnostic odds ratio for the diagnosis of early liver cancer are high. Therefore, the biomarkers PRL, EIF1AY, and PNPT1 of the present invention can be utilized in various ways in the field of early liver cancer diagnosis.

Inventors

  • 오세옥
  • 안지혜
  • 한명은
  • 박영목
  • 김효진
  • 조광우

Assignees

  • 부산대학교 산학협력단
  • 부산대학교병원

Dates

Publication Date
20260507
Application Date
20241031

Claims (11)

  1. A biomarker composition for diagnosing early liver cancer comprising one or more selected from the group consisting of PRL (Prolactin), EIF1AY (Eukaryotic translation initiation factor 1A, Y-linked), and PNPT1 (Polyribonucleotide nucleotidyltransferase 1).
  2. A biomarker composition for diagnosing early liver cancer, wherein the early liver cancer is stage 1 according to the AJCC/UICC (American Joint Committee on Cancer / International Union Against Cancer) staging system.
  3. A biomarker composition for diagnosing early liver cancer, wherein, in claim 1, the early liver cancer diagnosis is a method for distinguishing early liver cancer, hepatitis, and cirrhosis.
  4. A biomarker composition for diagnosing early liver cancer according to claim 1, wherein the PRL, EIF1AY, and PNPT1 are overexpressed in blood.
  5. A composition for diagnosing early liver cancer comprising a preparation for measuring the expression of one or more selected from the group consisting of PRL, EIF1AY, and PNPT1; or a gene encoding therefrom.
  6. A composition for diagnosing early liver cancer according to claim 5, wherein the preparation for measuring the expression is an oligopeptide, monoclonal antibody, polyclonal antibody, chimeric antibody, ligand, PNA (Peptide nucleic acid), or aptamer that specifically binds to PRL, EIF1AY, or PNPT1.
  7. A composition for diagnosing early liver cancer, wherein the preparation for measuring the expression is an antisense oligonucleotide, primer pair, or probe that specifically binds to a gene encoding PRL, EIF1AY, or PNPT1.
  8. An early liver cancer diagnostic kit comprising the composition of any one of claims 5 to 7.
  9. In claim 8, the above-mentioned early liver cancer diagnostic kit is an early liver cancer diagnostic kit that is an RT-PCR kit, a DNA chip kit, or a protein chip kit.
  10. A method for providing information on the diagnosis of early liver cancer, comprising the step of measuring the expression of one or more selected from the group consisting of PRL, EIF1AY, and PNPT1; or a gene encoding therefrom in a biological sample.
  11. (a) A step of treating a biological sample as an experimental group with a target substance to be screened; (b) a step of measuring and comparing the expression of one or more selected from the group consisting of PRL, EIF1AY, and PNPT1; or genes encoding therefrom; in the experimental group of step (a) above and the control group not treated with the target substance; and (c) a step of selecting a target substance that inhibits the expression of one or more selected from the group consisting of PRL, EIF1AY, and PNPT1 in the experimental group compared to the control group based on the result of the comparison in step (b) above; or a gene encoding the same; comprising a screening method for an early liver cancer treatment.

Description

Biomarker composition for early hepatocellular carcinoma diagnosis comprising PRL, EIF1AY and PNPT1 The present invention relates to biomarkers for the diagnosis of early liver cancer, namely PRL (Prolactin), EIF1AY (Eukaryotic translation initiation factor 1A, Y-linked), and PNPT1 (Polyribonucleotide nucleotidyltransferase 1). Liver cancer has a high mortality rate among cancers. According to Statistics Korea’s ‘2021 Statistics on Causes of Death,’ the number of deaths due to liver cancer was 20 per 100,000 people, ranking second in domestic cancer mortality. The reason for this poor prognosis is that, unlike other types of cancer, liver cancer generally has no noticeable symptoms. By the time patients visit a hospital due to symptoms such as jaundice, ascites, hepatic coma, or variceal bleeding, the cancer is usually diagnosed as advanced. Diagnosis of liver cancer has traditionally involved performing tissue biopsies or testing for liver cancer marker proteins, such as alpha-fetoprotein (AFP). Currently, AFP and PIVKA (Protein induced by vitamin K absence)-II are the most well-known biomarkers for diagnosis, prognosis assessment, and treatment evaluation; however, they have limitations in specificity and sensitivity. The utility of AFP in the diagnosis of hepatocellular carcinoma (HCC) is well-known. Regular AFP measurement is necessary not only for the diagnosis of advanced HCC but also for early detection, as HCC develops in 3–10% of patients with cirrhosis annually during its natural course. However, there are limitations in diagnosis because AFP expression increases not only in liver cancer but also in benign liver diseases such as chronic hepatitis and cirrhosis. Furthermore, in benign liver diseases, even if AFP levels rise, they tend to decrease over time, allowing the possibility of malignancy to be ruled out. However, since AFP expression can naturally decrease in the case of liver cancer (especially early-stage liver cancer less than 2 cm), there are limitations to excluding liver cancer based solely on the pattern of AFP changes. Therefore, there is a need for a tumor marker that can diagnose liver cancer more sensitively than AFP. Figure 1 shows the results of analyzing the expression of genes PRL, EIF1AY, PNPT1, UBD, B3GAT3, and AFP in liver cancer tissue using the TCGA Database. Figure 2 shows the results of confirming the expression of proteins PRL, EIF1AY, PNPT1, UBD, B3GAT3, and AFP in the blood of early liver cancer patients and liver disease patients using the Somascan method. Figure 3 shows the results of evaluating the 'effectiveness of early liver cancer diagnosis' of proteins (PRL, EIF1AY, PNPT1, UBD, B3GAT3, and AFP) as diagnostic biomarkers through AUC (area under curve) analysis. Figure 4 shows the results of confirming the specificity, sensitivity, and diagnostic odds ratio of early liver cancer for proteins (PRL, EIF1AY, PNPT1, UBD, B3GAT3, and AFP) and protein combinations (PRL, EIF1AY, and PNPT1). The present invention will be described in detail below. According to an embodiment of the present invention, the present invention provides a biomarker composition for diagnosing early liver cancer comprising one or more selected from the group consisting of PRL (Prolactin), EIF1AY (Eukaryotic translation initiation factor 1A, Y-linked), and PNPT1 (Polyribonucleotide nucleotidyltransferase 1). In the present invention, PRL (Prolactin) is a hormone secreted by the anterior pituitary gland that regulates the growth of various tissues. Additionally, PRL is involved in milk secretion and enhances viability by inhibiting apoptosis. In the present invention, EIF1AY (Eukaryotic translation initiation factor 1A, Y-linked) is a component of the 43S pre-initiation complex and plays an important role in finding the start codon by binding to the region around the mRNA cap and scanning the mRNA 5’ untranslated region. Together with the EIF1 protein, it promotes the formation of the 48S complex at the start codon region. In the present invention, PNPT1 (Polyribonucleotide nucleotidyltransferase 1) is a protein that has the activity of degrading RNA in the 3’ to 5’ direction in a 3’-to-5’ manner in a responsive manner and is involved in various RNA metabolisms. PNPT1 is mainly located in mitochondria and is involved in the translocation of 5S RNA and the RNA portion of ribonuclease P into the mitochondria, as well as the adenylation of mitochondrial mRNA. In a specific embodiment of the present invention, the PRL, EIF1AY, and PNPT1 may be used alone for the diagnosis of early liver cancer, or may be used in combination. That is, the biomarker composition for the diagnosis of early liver cancer according to the present invention may include PRL, may include EIF1AY, and may include PNPT1. Furthermore, the composition may include all three types (PRL, EIF1AY, and PNPT1) to improve the specificity, sensitivity, and diagnostic odds ratio of the diagnosis of early liver cancer. In this invention, unli