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Prognostic marker and prognostic risk assessment model for metastatic colon adenocarcinoma and application of prognostic marker and prognostic risk assessment model

A risk assessment model and prognostic marker technology, applied in the field of genetic technology and medicine, can solve the problem of not providing differential genes, and achieve the effect of good discrimination performance

Active Publication Date: 2020-12-29
杭州百可生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, the above studies mainly focused on the differentially expressed regulatory factors between tumor tissue and normal tissue, and did not provide information on differentially expressed genes only in metastatic COAD.

Method used

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  • Prognostic marker and prognostic risk assessment model for metastatic colon adenocarcinoma and application of prognostic marker and prognostic risk assessment model
  • Prognostic marker and prognostic risk assessment model for metastatic colon adenocarcinoma and application of prognostic marker and prognostic risk assessment model
  • Prognostic marker and prognostic risk assessment model for metastatic colon adenocarcinoma and application of prognostic marker and prognostic risk assessment model

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] The purpose of this example is to screen DEGs in patients with primary COAD and metastatic COAD.

[0070] (1) Screening DEmiRNAs and their target genes

[0071] In order to screen DEmiRNAs from the miRNA-Seq dataset of the TCGA database, differential expression analysis was performed using the Edger software package in this example.

[0072] In this database, 62 / 379 (16.4%) of DEmiRNAs came from patients with M1 stage, and 317 / 379 (83.6%) came from patients with M0 stage, where M0 means patients without distant metastasis, and M1 means patients with distant metastasis. The 14 DEmiRNAs with critical points |log2FC|>1 and p-valuefigure 1 As shown, as shown in Figure A, there are 8 up-regulated DEmiRNAs and 6 down-regulated DEmiRNAs, and the corresponding heat map, that is, the specific miRNAs are shown in Figure B;

[0073] The specific analysis is shown in Table 1 below.

[0074] Table 1

[0075]

[0076]

[0077] Meanwhile, 8918 potential target genes of 8 up-r...

Embodiment 2

[0086] The purpose of this example is to screen genes related to the prognosis of metastatic COAD.

[0087] (1) Functional annotation and enrichment analysis

[0088] In order to analyze the enrichment pathway of DEmiRNAs, KEGG pathway enrichment analysis was carried out using DIANA bioinformatics tool in this example. These 14 DEmiRNAs were significantly enriched in cancer- and metastasis-related pathways, such as cell cycle, adherens junctions, and p53 signaling pathways.

[0089] In addition, pathway and process enrichment analyzes were performed on the basis of 127 candidate DEGs.

[0090] The first 12 involved clusters such as image 3 As shown, they are:

[0091] I. NABA matrisome associated (NABA matrisome associated); II. Forebrain neuron differentiation; III. Cell-cell adhesion through plasma membrane adhesion molecules (Cell-cell adhesion); IV. Skin development (skin development); V, blood circulation; VI, peptide cross-linking; VII, nervous system; VIII, forelim...

Embodiment 3

[0112] This example uses prognostic markers for risk scoring and survival analysis, and compares the performance of individual genes versus combined gene signature panels.

[0113] (1) A gene signature panel with prognostic value for COAD was established using stepwise multiple Cox regression analysis. According to the results, the risk scoring system for each patient was calculated as follows:

[0114] Risk score = LEP × 0.134582 + REG3A × (-0.05402) + DLX2 × 0.211469;

[0115] Patients were then classified into low-risk (n178) groups according to the median risk score.

[0116] Such as Figure 4 As shown, compared with the low-risk group, the survival period of patients in the high-risk group was significantly worse (log-rank test, p value 0.01692, p value <0.05).

[0117] In order to evaluate the prognostic value of the risk score, the ROC curve of OS at 5 years was drawn and the AUC value was calculated in this embodiment.

[0118] From Figure 5 It can be seen from th...

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Abstract

The invention provides a prognostic marker and prognostic risk assessment model for metastatic colon adenocarcinoma and application of the prognostic marker and the prognostic risk assessment model. The prognostic marker comprises a combination of any one or at least two of prognostic related genes LEP, DLX2, CLSTN2 or REG3A. Meanwhile, the invention further provides three potential treatment drugs for the metastatic colon adenocarcinoma, namely ajmaline, TTNPB and dydrogesterone. The prognostic marker provided by the invention is remarkably related with the survival of a colon adenocarcinoma(COAD) patient, and the risk assessment model constructed by utilizing the prognostic marker can carry out risk assessment and survival analysis on patients, and the accuracy is relatively high.

Description

technical field [0001] The invention relates to the fields of gene technology and medicine, and relates to a prognostic marker, a prognostic risk assessment model and an application thereof for metastatic colon adenocarcinoma. Background technique [0002] Colon cancer is a common malignant tumor of the digestive tract that occurs in the colon, and distant metastasis accounts for a large proportion of colon cancer-related deaths. For metastatic colon cancer, although there are some treatment options for metastatic disease, such as fluoropyrimidine-based chemotherapy, anti-VEGF drugs, anti-EGFR drugs and Immunotherapy, etc. Metastatic colon cancer remains incurable in most cases. [0003] Colon adenocarcinoma (COAD) is the most common histological subtype of colon cancer, and its occurrence and development involve multiple complex pathological processes such as the environment, genes, cell types, cell signaling pathways, tissues and organs, and the regulation of the immune s...

Claims

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Application Information

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IPC IPC(8): C12Q1/6886C12N15/11G16H50/30
CPCC12Q1/6886G16H50/30C12Q2600/158C12Q2600/118C12Q2600/178C12Q2600/136
Inventor 于晓方
Owner 杭州百可生物科技有限公司
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