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
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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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