Investigating the impact of SMAD2 and SMAD4 downregulation in colorectal cancer and their correlation with immune markers, prognosis, and drug resistance and sensitivity.
Humans
Colorectal Neoplasms
/ genetics
Smad4 Protein
/ genetics
Smad2 Protein
/ genetics
Prognosis
Gene Expression Regulation, Neoplastic
/ drug effects
Drug Resistance, Neoplasm
/ genetics
Biomarkers, Tumor
/ genetics
Transforming Growth Factor beta
/ metabolism
Signal Transduction
/ genetics
Male
Down-Regulation
/ genetics
Female
Colorectal cancer
Survival of patients
TGF-β signaling pathway
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
22 Jul 2024
22 Jul 2024
Historique:
received:
11
04
2024
accepted:
03
06
2024
medline:
22
7
2024
pubmed:
22
7
2024
entrez:
22
7
2024
Statut:
epublish
Résumé
While many genes linked to colorectal cancer (CRC) contribute to cancer development, a thorough investigation is needed to explore crucial hub genes yet to be fully studied. A pivotal pathway in CRC is transforming growth factor-beta (TGF-β). This study aimed to assess SMAD2 and SMAD4 gene expression from this pathway. Counted data from the Cancer Genome Atlas (TCGA) were examined, comparing 483 tumor and 41 normal samples. Using clinical data, genes impacting overall survival (OS) were evaluated. GSE39582 was employed to confirmed the levels of genes in CRC compared to the normal samples. Additionally, employing unhealthy samples and the RT-qPCR means our outcomes was validated. Finally, PharmacoGx information were utilized to connect the levels of potential genes to drug tolerance and susceptibility. Our findings showed SMAD2 and SMAD4 levels in TGF-β signaling were more significant than other pathway genes. Our findings indicated that the protein levels of these genes were lower in malignant tissues than in healthy tissues. Results revealed a significant correlation between low levels of SMAD2 and unfavorable OS in CRC individuals. RT-qPCR results demonstrated decreased expressions of both SMAD2 and SMAD4 in cancer tissues compared to elevated levels in adjacent normal samples. Our results showed significant association between selected genes and immune cell infiltration markers such as CD8+, and B-cells. Our results indicated a potential association among the levels of SMAD2 and SMAD4 genes and tolerance and susceptibility to Nilotinib and Panobinostat drugs. Reduced expression of SMAD2 and SMAD4 may be pivotal in CRC progression, impacting downstream genes unrelated to patient OS. These findings suggest a potential role for SMAD2 and SMAD4 as predictive markers for drug response in CRC patients.
Sections du résumé
BACKGROUND
BACKGROUND
While many genes linked to colorectal cancer (CRC) contribute to cancer development, a thorough investigation is needed to explore crucial hub genes yet to be fully studied. A pivotal pathway in CRC is transforming growth factor-beta (TGF-β). This study aimed to assess SMAD2 and SMAD4 gene expression from this pathway.
METHODS AND RESULTS
RESULTS
Counted data from the Cancer Genome Atlas (TCGA) were examined, comparing 483 tumor and 41 normal samples. Using clinical data, genes impacting overall survival (OS) were evaluated. GSE39582 was employed to confirmed the levels of genes in CRC compared to the normal samples. Additionally, employing unhealthy samples and the RT-qPCR means our outcomes was validated. Finally, PharmacoGx information were utilized to connect the levels of potential genes to drug tolerance and susceptibility. Our findings showed SMAD2 and SMAD4 levels in TGF-β signaling were more significant than other pathway genes. Our findings indicated that the protein levels of these genes were lower in malignant tissues than in healthy tissues. Results revealed a significant correlation between low levels of SMAD2 and unfavorable OS in CRC individuals. RT-qPCR results demonstrated decreased expressions of both SMAD2 and SMAD4 in cancer tissues compared to elevated levels in adjacent normal samples. Our results showed significant association between selected genes and immune cell infiltration markers such as CD8+, and B-cells. Our results indicated a potential association among the levels of SMAD2 and SMAD4 genes and tolerance and susceptibility to Nilotinib and Panobinostat drugs.
CONCLUSION
CONCLUSIONS
Reduced expression of SMAD2 and SMAD4 may be pivotal in CRC progression, impacting downstream genes unrelated to patient OS. These findings suggest a potential role for SMAD2 and SMAD4 as predictive markers for drug response in CRC patients.
Identifiants
pubmed: 39037563
doi: 10.1007/s11033-024-09697-x
pii: 10.1007/s11033-024-09697-x
doi:
Substances chimiques
Smad4 Protein
0
SMAD4 protein, human
0
Smad2 Protein
0
SMAD2 protein, human
0
Biomarkers, Tumor
0
Transforming Growth Factor beta
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
831Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
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