Predictive biomarker for human colorectal cancer or human colorectal cancer metastasis and application of predictive biomarker

A biomarker and colorectal cancer technology, applied in the field of cytochrome C oxidase and predictive biomarker COX4I2, can solve the problems of insufficient metastasis prediction ability and low accuracy of biomarkers in colorectal cancer patients, and achieve The effect of promoting CRC progression and promoting activation

Pending Publication Date: 2022-07-05
JIANGSU PROVINCIAL HOSPITAL OF TCM
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Purpose of the invention: The technical problem to be solved by the present invention is to overcome the low accuracy of the biomarkers for the prognosis judgment of colorectal cancer patients in the existing clinical diagnosis and the insufficiency of the ability to predict the metastasis of colorectal cancer patients

Method used

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  • Predictive biomarker for human colorectal cancer or human colorectal cancer metastasis and application of predictive biomarker
  • Predictive biomarker for human colorectal cancer or human colorectal cancer metastasis and application of predictive biomarker
  • Predictive biomarker for human colorectal cancer or human colorectal cancer metastasis and application of predictive biomarker

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Example 1 Determination of valuable genes in cytochrome C oxidase

[0023] In the present study, all 42 cytochrome C oxidase-related genes were subjected to LASSO regression to determine the target genes for subsequent studies. Cross-validation is performed in 10 rounds to prevent overfitting ( figure 1 A and B). Continuous univariate and multivariate Cox regression analyses were performed, showing that both COX4I2 and COX19 were associated with CRC prognosis, identifying these genes as study targets ( figure 1 C-H).

Embodiment 2

[0024] Example 2 COX4I2 promotes the malignant phenotype of colorectal cancer

[0025] The present invention uses Western blotting and IHC (immunohistochemistry) to explore the expression of COX4I2 in CRC tissue, indicating that the level of COX4I2 in CRC cells and tissues is very high. The mean H-SCOREs of COX4I2 expression in CRC and paired control tissues were 95.53 ± 15.96 and 19.14 ± 6.65 ( figure 2 A-C). The levels of COX4I2 were highest in the RKO and SW480 cell lines, so these cell lines were used for further studies. The efficiency of transfection was confirmed by GFP expression and Western blotting ( figure 2 D). Silencing COX4I2 reduces clone formation ( figure 2 E). Furthermore, stable COX4I2 overexpression led to the successful formation of xenograft tumors in mice ( figure 2 F-H). Ki-67 (a nuclear proliferation marker, which is an indicator of tumor cell proliferation activity) is a known prognostic factor in CRC, and its strong expression is associate...

Embodiment 3

[0026] Example 3 Overexpressed COX4I2 promotes the EMT process

[0027] GSEA and single-cell RNA-Seq analysis showed that the expression of COX4I2 was closely related to the epithelial-mesenchymal transition (EMT) of cells. An increase in EMT-related phenotypes was found to be associated with COX4I2 overexpression. This effect was reduced after treatment with the integrin FGF1-specific inhibitor PD-166866 ( image 3 A-B). TIMER analysis also found that the expression of COX4I2 was significantly correlated with N-cadherin (CDH2) (R=0.320, P image 3 D).

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Abstract

The invention discloses an application of a cytochrome C oxidase subunit 4 subtype 2 (COX4I2) in preparation of a predictive biomarker for prognosis and immunotherapy reactivity of a human colorectal cancer patient. The correlation between the COX4I2 level and clinical characteristics and biological effects thereof is evaluated in vitro and in vivo, it is found that rising of the COX4I2 level is related to poor prognosis of a patient suffering from the colorectal cancer, experimental research further observes that COX4I2 can participate in epithelial-mesenchymal transition (EMT) of colorectal cancer cells, expression of fibroblast growth factor 1 (FGF1) is promoted, and the COX4I2 can be used for treating the poor prognosis of the patient suffering from the colorectal cancer. Tumor-related fibroblasts are activated and recruited; and tumor angiogenesis is promoted. Therefore, the COX4I2 can be used as a prognosis biomarker of a colorectal cancer patient, and can also be a new target for treatment development.

Description

technical field [0001] The invention relates to a cytochrome C oxidase, relates to a predictive biomarker COX4I2 for the prognosis of human colorectal cancer, and belongs to the technical field of biomedicine. Background technique [0002] Colorectal cancer (CRC) is a common digestive tract tumor with the third highest incidence among malignant tumors and the second highest mortality among cancers. Its pathogenesis is complex, involving numerous susceptibility factors, and is related to heredity, diet and living habits. Statistics show that 30%-50% of CRC tumors recur after surgery and have distant metastases, especially in the liver, lungs, bones and ovaries, and the five-year survival rate often does not exceed 10%. [0003] Tumor growth and metastasis require vascular nourishment, and tumor neovascularization is a feature of the tumor microenvironment. The hypoxic microenvironment disrupts the balance of vascular-related factors, activates endothelial cells, increases v...

Claims

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Application Information

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IPC IPC(8): G01N33/574G01N33/573C12N9/02
CPCG01N33/57484G01N33/57419G01N33/573C12N9/0053C12Y109/03001G01N2333/90216
Inventor 邹玺李洁玭刘沈林陈玉根刘元杰曾树宏
Owner JIANGSU PROVINCIAL HOSPITAL OF TCM
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