Application of PINK1 as marker for predicting sensitivity of lung adenocarcinoma to MAPK inhibitor and recurrence of lung adenocarcinoma

An inhibitor and sensitive technology, applied in the field of biomedical technology and biomedicine, can solve the problems of MAPK pathway inhibitor drug resistance, and achieve the effect of improving tumor dormancy and recurrence, preventing tumor recurrence, and avoiding drug resistance and tumor recurrence.

Pending Publication Date: 2022-05-13
SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In addition, whether drug-induced tumor dormancy contributes to resistance to MAPK pathway inhibitors in lung adenocarcinoma patients has not yet been studied.

Method used

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  • Application of PINK1 as marker for predicting sensitivity of lung adenocarcinoma to MAPK inhibitor and recurrence of lung adenocarcinoma
  • Application of PINK1 as marker for predicting sensitivity of lung adenocarcinoma to MAPK inhibitor and recurrence of lung adenocarcinoma
  • Application of PINK1 as marker for predicting sensitivity of lung adenocarcinoma to MAPK inhibitor and recurrence of lung adenocarcinoma

Examples

Experimental program
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Effect test

Embodiment 1

[0068] Example 1 Correlation between the expression of PINK1 and tumor recurrence in patients with lung adenocarcinoma

[0069] In order to verify the relationship between the expression of PINK1 and the recurrence and survival prognosis of patients with lung adenocarcinoma, this study used the PINK1 antibody (23274-1-AP, proteintect) to perform immunohistochemistry on tissue chips (Shanghai Xinchao Biotechnology Co., Ltd.) of 90 patients with lung adenocarcinoma. According to the staining intensity and positive rate of PINK1, the expression grade of PINK1 was judged. Divided into 4 grades: grade 1 represents no coloration, grade 2 represents weak positive, grade 3 represents positive, and grade 4 represents strong positive. The patients were divided into groups according to the recurrence status, and the expression of PINK1 in the tumor tissues of the two groups of patients was counted.

[0070] The statistical results showed that the expression of PINK1 protein was higher i...

Embodiment 2

[0071] Example 2 Study on the effect of PINK1 expression on the dormancy of lung adenocarcinoma at the cell level

[0072] 1. Correlation analysis between PINK1 expression and cell cycle regulation gene expression

[0073] The data comes from the RNA sequencing data of 503 cases of lung adenocarcinoma in the TCGA database, and the expression of the PINK1 gene and the expression of cell cycle regulatory genes are obtained, including the genes PCNA, MKi67, CDK1, and CDK2 that positively regulate the cell cycle, and the genes that negatively regulate the cell cycle. Genes such as CDKN1A, CDKN1C.

[0074] The results were tested by Pearson, and the results showed that the expression of PINK1 gene was significantly positively correlated with the expression of negatively regulated genes of cell cycle, and was significantly negatively correlated with the expression of positively regulated genes of cell cycle ( figure 2 A), which shows that PINK1 is a negative regulator of the cell ...

Embodiment 3

[0104] Example 3 Study on the effect of PINK1 expression on the efficacy of MAPK pathway inhibitors in the treatment of lung adenocarcinoma at the cell level

[0105] 1. Correlation analysis between the expression of PINK1 and the sensitivity of lung adenocarcinoma cell lines to MAPK pathway inhibitors The data came from the Genomics of drug sensitivity in cancer (GDSC) database. Expression of the PINK1 gene in lung adenocarcinoma cell lines. The lung adenocarcinoma cell lines were divided into two groups according to PINK1 expression: the top 20% of PINK1 expression cells, i.e. high PINK1 expressing cells, and the post PINK1 expression 20% cells, i.e. low PINK1 expressing cells. The median lethal concentration data (IC50) of 11 MAPK pathway inhibitors on lung adenocarcinoma cell lines were obtained from this database. Comparing the differences in the sensitivity of cells to MAPK pathway inhibitors between the high-expression PINK1 group and the low-expression PINK1 group, th...

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Abstract

The invention discloses application of PINK1 as a marker for predicting sensitivity of lung adenocarcinoma to an MAPK inhibitor and recurrence of lung adenocarcinoma. Through experiments, it is found that expression increase of PINK1 in tumors prompts that a lung adenocarcinoma patient has higher tumor dormancy and recurrence risks, so that dormancy and recurrence of lung adenocarcinoma can be predicted by detecting the expression level of PINK1 in the lung adenocarcinoma patient, and the blank of biomarkers for dormancy and recurrence of lung adenocarcinoma in the prior art is filled up; the expression level of PINK1 can be used as a judgment standard for lung adenocarcinoma dormancy and recurrence, and is used for developing a lung adenocarcinoma dormancy and recurrence prediction kit. Besides, for a lung adenocarcinoma patient receiving the MAPK pathway inhibitor, the increase of the expression of the PINK1 prompts that the risk of drug resistance and relapse is increased after the patient is treated, so that intervention measures can be taken in advance clinically, tumor relapse is prevented, and a new strategy and thought are provided for clinically treating the lung adenocarcinoma.

Description

technical field [0001] The invention relates to the fields of biomedical technology and biomedicine, in particular to the application of PINK1 as a marker for predicting the sensitivity of lung adenocarcinoma to MAPK inhibitors and the recurrence of lung adenocarcinoma. Background technique [0002] Lung cancer is one of the common tumors that endanger human health, and the mortality rate of lung cancer ranks first among malignant tumors. Non-small cell lung cancer accounts for 80% to 85% of all lung cancers, and lung adenocarcinoma is the most common histological type in non-small cell lung cancer. Treatment for lung cancer includes surgical resection, chemotherapy, radiation, and targeted therapy. Even with the continuous improvement of treatment methods, the 5-year survival rate of lung adenocarcinoma patients is still very low. Among patients with early-stage lung adenocarcinoma who undergo complete surgical resection, approximately 30% experience tumor recurrence. In...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N9/12C12N15/54C12N15/867C12Q1/6886G01N33/574G01N33/68A61K45/00A61K45/06A61P35/00A61P35/04
CPCC12N9/12C12Y207/11C12N15/86C12Q1/6886G01N33/57423G01N33/57484G01N33/68A61K45/00A61K45/06A61P35/00A61P35/04C12N2740/15043C12N2740/15052C12Q2600/158C12Q2600/118C12Q2600/106G01N2800/54G01N2800/52G01N2800/50
Inventor 尹东李贇陈恒星
Owner SUN YAT SEN MEMORIAL HOSPITAL SUN YAT SEN UNIV
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