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CN-116622841-B - Molecular marker for lung cancer diagnosis, chemotherapy or prognosis detection and application thereof

CN116622841BCN 116622841 BCN116622841 BCN 116622841BCN-116622841-B

Abstract

The invention discloses a molecular marker for lung cancer diagnosis, chemotherapy or prognosis detection and application thereof, and relates to the technical field of molecular diagnosis. Molecular markers include trypsin 3 splice variant 3 and transcription factor bone marrow zinc finger gene 1 splice variant 2. By detecting the expression level of MZF1-V2 and PRSS3-V3 genes, lung cancer diagnosis, chemotherapy or prognosis detection is further realized. The molecular marker has important scientific significance and clinical value in the application of individuation accurate treatment for improving the chemosensitivity, not only provides an effective molecular target for individuation accurate treatment of lung cancer patients, but also provides a new basis for intervention new strategies. In addition, the proposal of the molecular marker also provides a more reliable lung cancer diagnosis and prognosis prediction means.

Inventors

  • LIN SHUYE
  • HUANG JIAQIANG

Assignees

  • 首都医科大学附属北京胸科医院
  • 北京市结核病胸部肿瘤研究所

Dates

Publication Date
20260505
Application Date
20220214

Claims (5)

  1. 1. The application of a substance for detecting a molecular marker in preparing a non-small cell lung cancer diagnosis detection preparation is characterized in that the molecular marker comprises a trypsin 3 splice variant 3 and a transcription factor bone marrow zinc finger gene 1 splice variant 2, the nucleotide sequence of the trypsin 3 splice variant 3 is shown as SEQ ID NO.1, and the nucleotide sequence of the transcription factor bone marrow zinc finger gene 1 splice variant 2 is shown as SEQ ID NO. 2.
  2. 2. The use according to claim 1, wherein the substance is a primer or reagent for detecting the molecular marker.
  3. 3. The use according to claim 2, wherein the sequence of the primer for detecting the trypsin 3 splice variant 3 is shown in SEQ ID NO.3-4 and the sequence of the primer for detecting the transcription factor bone marrow zinc finger gene 1 splice variant 2 is shown in SEQ ID NO. 5-6.
  4. 4. The application of a substance for detecting a molecular marker in preparing a non-small cell lung cancer diagnosis kit is characterized in that the molecular marker comprises a trypsin 3 splice variant 3 and a transcription factor bone marrow zinc finger gene 1 splice variant 2, the nucleotide sequence of the trypsin 3 splice variant 3 is shown as SEQ ID NO.1, and the nucleotide sequence of the transcription factor bone marrow zinc finger gene 1 splice variant 2 is shown as SEQ ID NO. 2.
  5. 5. The use according to claim 4, wherein the substance is a primer or a reagent for detecting the molecular marker, the primer sequence for detecting the trypsin 3 splice variant 3 is shown in SEQ ID NO.3-4, and the primer sequence for detecting the transcription factor bone marrow zinc finger gene 1 splice variant 2 is shown in SEQ ID NO. 5-6.

Description

Molecular marker for lung cancer diagnosis, chemotherapy or prognosis detection and application thereof Technical Field The invention relates to the technical field of molecular diagnosis, in particular to a molecular marker for lung cancer diagnosis, chemotherapy or prognosis detection and application thereof. Background Lung cancer is a global high-grade tumor, and is the first place of malignant tumor onset in China. In 2015, the new cases of lung cancer in China are about 78.7 tens of thousands, accounting for 20.03% of the new cases of malignant tumor, and the death number is about 63.1 tens of thousands, accounting for 26.99% of the new cases of malignant tumor. Among them, non-SMALL CELL lung cancer (NSCLC) is the most common histological type of lung cancer, and about 85% (Sung H,Ferlay J,Siegel RL,et al.Global Cancer Statistics 2020:GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36Cancers in 185Countries.CA Cancer J Clin 2021,71(3):209-249.). of lung cancer patients have low survival rate of lung cancer patients in 5 years due to hidden early symptoms, easy metastasis and lack of effective monitoring means when most patients are diagnosed in middle and late stages. The amplification or mutation of oncogenes and the silencing and loss of function of tumor suppressor genes caused by genetic variation and epigenetic disorders play an important role in the progression of lung cancer. The progressive and reversible nature of epigenetic changes during tumorigenesis is of great importance for early detection and targeted treatment of lung cancer compared to genetic mutations. At present, the research is clear that the abnormal expression and dysfunction of the gene caused by the abnormal change of CpG island methylation and histone modification of the promoter region, especially the hypermethylation of the cancer suppressor gene promoter region, has been used as an epigenetic marker and a drug target to be applied to the aspects of molecular diagnosis, treatment, prognosis evaluation and the like of diseases such as tumors (Oh JH,Jung SH,Hong SJ,and Rhyu MG,DNA Methylation as Surrogate Marker For Gastric Cancer.J Cancer Prev 20:172-178,2015.). Human trypsin (trypsin) plays an important role in a variety of physiological and pathological processes and is a novel molecular target through specific functions of regulating the activity of other proteins to participate in cancer progression. Various studies have directed to the association of the trypsin precursor molecule serine protease 3 (PRSS 3) with tumors, PRSS3 inhibitors have been developed to prevent their carcinomatous effects (Hockla A,Miller E,Salameh Ma et al,.PRSS3/mesotrypsin is a therapeutic target for metastatic prostate cancer.Molecular cancer research:MCR 2012,10(12):1555-1566.Radisky ES.PRSS3/mesotrypsin in prostate cancer progression:implications for translational medicine.Asian journal of andrology 2013,15(4):439-440.). However, whether PRSS3 is used as a pro-cancer factor to promote tumor metastasis and recurrence, or as a cancer inhibitor to inhibit tumor growth, its biological function in malignant tumors has not been theorized. There are opposite reports on PRSS3 expression and function even in the same type of tumor, such as non-small cell lung cancer. In one aspect, the study shows that increased expression of PRSS3 in metastatic NSCLC cells and that increased expression of PRSS3 is associated with a poor prognosis in the patient. However, on the other hand, studies have shown that PRSS3 exhibits apparent silencing in NSCLC and promotes proliferation and metastasis of cells, has potential oncogene-like effects, and is associated with PRSS3 exhibiting abnormal hypermethylation (Ma H,Hockla A,Mehner C,Coban M,Radisky ES.PRSS3/Mesotrypsin and kallikrein-related peptidase 5are associated with poor prognosis and contribute to tumor cell invasion and growth in lung adenocarcinoma.Scientific Reports 2019,9(1):1844.Marsit CJ,Chinedu O,Hadi D,Kelsey KT.Epigenetic silencing of the PRSS3 putative tumor suppressor gene in non-small cell lung cancer.Molecular Carcinogenesis 2010,44(2):146-150.). These studies indicate that the expression pattern and functional phenotype of PRSS3 during tumorigenesis and progression exhibit a controversial "two-way" effect and are believed to be caused by the different PRSS3 expression and signaling pathways due to the different sources of tissue cells and their tumor microenvironment. Because of the high sequence consistency of PRSS3 splice variants, specific antibodies and accurate detection methods for each isomer are lacking, and the specific type of splice variants and isomers of PRSS3 abnormal expression in tumors cannot be further determined according to literature reports, which suggests that the expression and functions of PRSS3 in the process of tumorigenesis and development and the molecular mechanism thereof need further intensive system research. Therefore, research on the regulation and