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Novel marker of epithelial-mesenchymal transition in pancreatic cancer

A pancreatic cancer and epithelial technology, which is applied in the field of evaluating the epithelial-mesenchymal transition ability of pancreatic cancer, can solve the problems of clinical application, unidentified metastasis, recurrent gene mutation, and inability to obtain sufficient effects.

Pending Publication Date: 2021-10-12
TOHOKU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, efforts have been made so far to research RAS-targeting inhibitors such as competitive inhibitors of RAS and GTP. However, due to the presence of high concentrations of GTP, GDP, etc. in cells, sufficient effects cannot be obtained, and none of them have been clinically used.
[0004] Therefore, although it is important to further elucidate the malignant mechanism of pancreatic cancer, gene mutations specific to metastasis and recurrence have not yet been identified.
In addition, gene expression fluctuations and signal transduction changes in primary tumors that are acquiring metastatic ability, and thus metastasis-promoting factors, take into account the self-replication of cancer cells, epithelial-mesenchymal transition, and the influence of the surrounding environment of cancer, but it has not yet been established. there are many unknowns

Method used

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  • Novel marker of epithelial-mesenchymal transition in pancreatic cancer
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  • Novel marker of epithelial-mesenchymal transition in pancreatic cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0099] Computer simulation (in silico) study of the relationship between BACH1 expression level and prognosis

[0100] It was investigated whether the expression level of BACH1 in pancreatic cancer patient test samples registered in The Cancer Genome Atlas (TCGA) database is associated with prognosis. The RNA-sequence clinical data of 176 pancreatic cancer patients were obtained from the TCGA database, and the cut-off value was obtained according to the Receiver Operating Characteristic (ROC) curve based on the clinical data by using the software JMP pro v13.1.0. Based on the cut-off value, the BACH1 low expression group (n=134) and high expression group (n=42) were divided into two groups ( figure 1 The left panel of A), the overall survival rate (Overall survival, OS) was analyzed using the multiplication limit method.

[0101] The results show that: in the BACH1 high expression group, OS will be significantly reduced (log rank test; Pfigure 1 Right panel of A). This resu...

Embodiment 2

[0102] Research on the expression of BACH1 in pancreatic cancer clinical test samples

[0103] In order to investigate the relationship between the expression of BACH1 protein and the prognosis, using the clinical test samples of pancreatic cancer undergoing surgery in the Gastrointestinal Department of Tohoku University Hospital, Japan, anti-human BACH1 monoclonal antibody (9D11, self-made antibody, dilution (dilution) 1 : 100) immunohistochemistry. The clinical detection samples of pancreatic cancer were selected from 116 cases of pancreatic cancer who underwent resection in the Department of Gastrointestinal Surgery of Northeastern University Hospital from 2007 to 2014. It should be noted that the specificity of the anti-human BACH1 monoclonal antibody has been confirmed by experiments using knockdown and knockout cells (data not disclosed).

[0104]Immunohistochemistry was performed using an anti-human BACH1 monoclonal antibody. The paraffin-embedded sections fixed with...

Embodiment 3

[0105] The relationship between the expression of BACH1 and the overall survival rate

[0106] To investigate the relationship between BACH1 protein expression and prognosis based on immunohistochemical classification, OS was analyzed using the multiplication limit method.

[0107] It was found that: consistent with the relationship between the expression of BACH1 and prognosis using the clinical data registered in the TCGA database, in the high expression group of BACH1 protein, OS was significantly reduced (log rank test; P=0.0213), BACH1 was the key factor for pancreatic cancer poor prognostic factor ( figure 1 C).

[0108] The results of univariate analysis showed that in OS, lymph node metastasis (P=0.0094), distant metastasis (P=0.0004), and BACH1 expression (P=0.0231) showed significance as prognostic factors. Therefore, tissue grade (P=0.0638) was added to these prognostic factor candidates, and multivariate analysis based on the Cox proportional hazards model was p...

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Abstract

To clarify the pancreatic cancer malignant alteration mechanism by BACH1, the present inventors disclosed a change in gene expression depending on the expression amount of BACH1 in a pancreatic cancer cell line by an RNA sequencing method. As the results of in vitro examinations on migration capability and infiltration capability and an in vivo orthotropic implantation test, the present inventors further indicated that BACH1 is usable, either alone or in combination with FOXA1 that is a downstream regulatory factor thereof, as an excellent biomarker of epithelial-mesenchymal transition in pancreatic cancer.

Description

technical field [0001] The present invention relates to a method for evaluating the ability of epithelial-mesenchymal transition (Epithelial mesenchymaltransitions, EMT) of pancreatic cancer, a method for evaluating the ability of metastasis or invasion of pancreatic cancer, a method for predicting the prognosis of pancreatic cancer, and A cancer metastasis inhibitor, and a screening method for a pancreatic cancer metastasis inhibitor. Background technique [0002] Pancreatic cancer is a cancer that mainly occurs in the epithelium of the pancreatic duct. The five-year survival rate after diagnosis is less than 10%, and it is the cancer with the worst prognosis. Surgical resection is the only treatment that can expect a radical cure, but from the current situation, it is difficult to detect early, 80% of cases are inoperable at the time of diagnosis, and the degree of malignancy is high, so chemotherapy has little effect, etc., and there is a lack of effective diagnosis. met...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6897C12N15/12
CPCC12Q2600/158C12Q1/6886C12N15/113C12N2310/20C12N2310/14
Inventor 五十岚和彦松本光代佐藤正规西泽弘成
Owner TOHOKU UNIV
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