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Colorectal cancer (CRC) is the most common cancer and one of the leading causes of cancer-related deaths worldwide
Advances in biomarker screening technology have greatly helped the clinical discovery of reliable new diagnostic and prognostic biomarkers for the early detection and treatment of CRC
diagnosis
Recently, microarray technology is very popular among scientists because it can screen out thousands of differently expressed messenger RNA (mRNA), microRNA and long non-coding RNA (lncRNA), which play a role in the development of diseases.
In this study, the researchers conducted a PubMed-based search to identify all studies using GEO-based CRC microarray expression data sets to explore central genes
Enrichment analysis of KEGG pathway showed that all 210 central genes extracted were significantly enriched in various pathways, including "Chemokine signaling pathway", "cancer pathway", "cell cycle", and "PI3K-Akt signaling pathway" , And the cytokine-cytokine receptor interaction pathway
Inflammation is an important part of the tumor microenvironment and one of the hallmarks of cancer
immunity
The identified true central gene CXCL12 can bind to CXCR4, which is a G protein-coupled receptor (GPCR) and is recognized as a factor related to cancer metastasis
CXCL12 serves as a new potential diagnostic biomarker for down-regulation in CRC patients of different races, cancer stages, genders, age groups and weights
The true central gene CXCL8, also known as neutrophil activating factor (NAF), and interleukin 8 (IL-8), was the first chemotherapy inducer identified as a leukocyte chemotherapy attractant
CXCL8 is a new potential diagnostic biomarker for CRC patients of different races, cancer stages, genders, age groups and weights
The real center of the gene ATG ( vascular angiotensin) is an important part angiotensin system (RAS) in the kidney, it is a powerful regulator of blood pressure
Blood vessel
In general, ATG serves as a new type of potential diagnostic biomarker for up-regulation in CRC patients of different races, cancer stages, genders, age groups, and weights
ATG is used as a new type of potential diagnostic biomarker for up-regulation in CRC patients of different races, cancer stages, genders, age groups and weights
The true hub gene GNB1 of G+ encodes 1, which is the β (β) subunit of the citrulline nucleotide-binding protein , which forms a heterogeneous complex with the G protein subunit, α and γ
1.
The upregulation of GNB1 can be considered as a new potential diagnostic biomarker for CRC patients of different races, cancer stages, genders, age groups and weights
The true hub gene GNG4 encodes the γ subunit of the G protein trimmer, which may act as a positive regulator of the RAS pathway, responsible for maintaining cell proliferation, cell adhesion and cell migration
.
Current research shows that CRC patients of different races, cancer stages, genders, age groups, and weights are significantly overexpressed at the mRNA level (p<0.
05)
.
The results of this study also show that the conversion level of GNG4 in COAD patients is up-regulated relative to the control group
.
It was further reported that GNG4 was significantly hypermethylated in the COAD patient population than in the control group, and a small amount (1%) of genetic changes was also made in the COAD sample
.
GNG4 overexpression and hypermethylation scenarios challenge the classic view that hypermethylation is always associated with downregulation
.
In conclusion, the results of this study show that GNG4 has new potential as a new potential diagnostic biomarker for CRC patients of different races, cancer stages, genders, age groups, and weights
.
.
The true central gene Chemokine (CXC pattern) ligand 1 (CXCL1), also known as GRO-α, belongs to the family of G protein-coupled receptors.
It specifically binds to CXC chemotherapy cytokine receptor 2, which activates cell proliferation.
RAS (Rat Sarcoma) pathway
.
This study determined a significant (p<0.
05) upregulation of CXCL1 mRNA in COAD patients of different races, cancer stages, gender, age groups, and weights
.
In addition, it also showed that compared with the control group, the conversion level of COAD patients increased the level of regulation of CXCL1
.
The correlation analysis between CXCL1 expression and methylation status revealed an expected significant (p<0.
05) negative correlation, which strengthened the role of dimethylation in the upregulation of CXCL1
.
Finally, the results of CXCL1 gene change analysis showed that CXCL1 expression is unlikely to be the effect of genetic changes, because the changes are noticed in a very small proportion (0.
4%) of COAD patients
.
In general, CXCL1 improves regulation as a new potential diagnostic biomarker for CRC patients of different races, cancer stages, genders, age groups, and weights
.
The cross talk details between the real central genes relate to the path to Crc in the background
.
At the cellular level, CXCL1, CXCL8, or CXCL12 bind to GPCRs (CXCR1, CXCR2, or CXCR4) and activate G protein
.
In this study, the up-regulation of GPCR ligands (CXCL1 and CXCL8) and G protein subunits (β and γ) should jointly up-regulate various downstream pathways
.
On the other hand, β and γ G protein subunits further up-regulated the Rho-GTPase family and Raf-1/MAP/Erk signaling cascade in this study
.
OS survival analysis of true central genes showed that high expression of GNG4 is a good prognostic biomarker, while CXCL12, CXCL8, AGT, GNB1 and CXCL1 are poor prognostic biomarkers for predicting the duration of operating system in COAD patients
.
In order to further clarify the basic mechanism of the true central gene in CRC tumors, this study conducted a correlation analysis between the expression of the true central gene and the penetration of CD8+T immune cells in COAD
.
CD8+ T immune cell penetration is used as a diagnostic marker for early detection of laryngeal squamous cell carcinoma, abbreviated as LSCC
.
This result shows that there is a significant positive correlation between the mRNA expression levels of CXCL12, GNB1, CXCL1 and CD8+ T immune cells and the penetration of C8+ T immune cells (p>0.
05), while the mRNA expression of CXCL8, AGT and GNG4 is correlated with CD8+ T There is a significant negative correlation between the infiltration of immune cells (p>0.
05)
.
Taken together, this is some correlation between the penetration by regulating CD8 + T immune cells, revealing new aspects of the real center of CRC tumor gene, these correlations may lead to a new direction for the treatment of patients with CRC
.
These correlations may bring new directions for the treatment of CRC patients
.
miRNAs are small non-coding RNA molecules (+22 nucleotides) responsible for the degradation and translation of mRNA in plants and animals
.
In CRC, it was found that there was a difference in the expression pattern of reported miR-1-3p
.
In view of the results of this study, we speculate that the four true central genes (CXCL8, CXCL12, CXCL1, and GNB1) are used as the production and down-regulation of mir-1-3p, which may cause these genes to act as different axes (mir-1-3p).
/CXCL8 or CXCL12, CXCL1 and GNB1) up-regulate in the pathogenesis of CRC
.
This study is the first to report the tumor effects of mir-1-3p and CXCL8, CXCL12, CXCL1 and GNB1 in CRC
.
In addition, we have also discovered that various drugs can be used to treat CRC by regulating the expression of true central genes
.
Real hub gene-drug interaction network to identify real hub genes
Panel AF represents the chemotherapeutic drugs available in CTD, which can reduce or increase the expression level of the true central gene
.
(A) CXCL12 real central gene drug network: (B) CXCL8 real central gene drug network: (C) AGT real central gene drug network: (D) GNB1 real central gene drug network: (E) GNG4 real Central Gene Drug Network: (F) CXCL1 The true Central Gene Drug Network
.
The red arrows indicate chemotherapeutic drugs that can increase the expression level of true central genes, and the green arrows indicate chemotherapeutic drugs that may decrease the expression levels of true central genes
.
The number of arrows between the chemotherapeutic drug and the true central gene in the network represents the amount of support from previous studies in the literature
.
In summary, we have identified a group of six differently expressed true central genes (central gene cluster genes), including CXCL12, CXCL8, AGT, GNB1, GNG4 and CXCL1, and their potential molecular pathways.
These genes can be used as The possible diagnosis and prognostic biomarkers of CRC patients of different races, cancer stages, genders, and age groups may help overcome heterogeneity and specific barriers
.
However, before clinical application, extensive biological investigations are needed, especially for the underrepresented populations in the expression data set used in this study
.
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