Comprehensive analysis of Syk gene methylation in colorectal cancer

Bu, Fanqin; Zhu, Xiaojian; Liu, Sicheng; Kang, Lin; Zhu, Jinfeng; Huang, Jun

doi:10.1002/iid3.449

Cited by 5 publications

(2 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We further explored the relationship between tumor-infiltrating immune cells and the risk score with seven common acceptable methods of estimating the infiltrating immune cells, including TIMER (Bu F, 2021), CIBERSORT ( Bu et al, 2021 ), xCell ( Oshi et al, 2021 ), quanTIseq ( Finotello et al, 2019 ), MCPcounter ( Li et al, 2021 ), EPIC ( Zeng et al, 2021 ), and CIBERSORT-ABS ( Tamminga et al, 2020 ). The synthetical analysis showed that the risk score was more positively related to tumor-infiltrating immune cells.…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization, Tumor Microenvironment Association, and Drug Susceptibility of DNA Methylation-Driven Genes in Renal Cell Carcinoma

Wang

Zhang

Hou

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Accumulating evidence suggests that DNA methylation has essential roles in the development of renal cell carcinoma (RCC). Aberrant DNA methylation acts as a vital role in RCC progression through regulating the gene expression, yet little is known about the role of methylation and its association with prognosis in RCC. The purpose of this study is to explore the DNA methylation-driven genes for establishing prognostic-related molecular clusters and providing a basis for survival prediction. In this study, 5,198 differentially expressed genes (DEGs) and 270 DNA methylation-driven genes were selected to obtain 146 differentially expressed DNA methylation-driven genes (DEMDGs). Two clusters were distinguished by consensus clustering using 146 DEMDGs. We further evaluated the immune status of two clusters and selected 106 DEGs in cluster 1. Cluster-based immune status analysis and functional enrichment analysis of 106 DEGs provide new insights for the development of RCC. To predict the prognosis of patients with RCC, a prognostic model based on eight DEMDGs was constructed. The patients were divided into high-risk groups and low-risk groups based on their risk scores. The predictive nomogram and the web-based survival rate calculator (http://127.0.0.1:3496) were built to validate the predictive accuracy of the prognostic model. Gene set enrichment analysis was performed to annotate the signaling pathways in which the genes are enriched. The correlation of the risk score with clinical features, immune status, and drug susceptibility was also evaluated. These results suggested that the prognostic model might be a promising prognostic tool for RCC and might facilitate the management of patients with RCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular Characterization, Tumor Microenvironment Association, and Drug Susceptibility of DNA Methylation-Driven Genes in Renal Cell Carcinoma

Wang

Zhang

Hou

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…A lower SYK protein expression and methylation are also connected with the metastasis of other cancer, including lung cancer, liver cancer, oral squamous cell cancer, pancreatic cancer, bladder cancer, gastric cancer, and urinary cancer [ 7 , 8 , 9 ]. Here, colorectal cancer (CRC) is also associated with this gene, and the loss of its expression is found in several CRC tissues [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Analysis of SYK Gene as a Prognostic Biomarker and Suggested Potential Bioactive Phytochemicals as an Alternative Therapeutic Option for Colorectal Cancer: An In-Silico Pharmaco-Informatics Investigation

Biswas¹,

Dey

Rahman

et al. 2021

JPM

View full text Add to dashboard Cite

Background: SYK gene regulates the expression of SYK kinase (Spleen tyrosine kinase), an important non-receptor protein-tyrosine kinase for immunological receptor-mediated signaling, which is also considered a tumor growth metastasis initiator. An onco-informatics analysis was adopted to evaluate the expression and prognostic value of the SYK gene in colorectal cancer (CRC), the third most fatal cancer type; of late, it may be a biomarker as another targeted site for CRC. In addition, identify the potential phytochemicals that may inhibit the overexpression of the SYK kinase protein and minimize the human CRC. Materials & Methods: The differential expression of the SYK gene was analyzed using several transcriptomic databases, including Oncomine, UALCAN, GENT2, and GEPIA2. The server cBioPortal was used to analyze the mutations and copy number alterations, whereas GENT2, Gene Expression Profiling Interactive Analysis (GEPIA), Onco-Lnc, and PrognoScan were used to examine the survival rate. The protein-protein interaction network of SYK kinase and its co-expressed genes was conducted via Gene-MANIA. Considering the SYK kinase may be the targeted site, the selected phytochemicals were assessed by molecular docking using PyRx 0.8 packages. Molecular interactions were also observed by following the Ligplot+ version 2.2. YASARA molecular dynamics simulator was applied for the post-validation of the selected phytochemicals. Results: Our result reveals an increased level of mRNA expression of the SYK gene in colorectal adenocarcinoma (COAD) samples compared to those in normal tissues. A significant methylation level and various genetic alterations recurrence of the SYK gene were analyzed where the fluctuation of the SYK alteration frequency was detected across different CRC studies. As a result, a lower level of SYK expression was related to higher chances of survival. This was evidenced by multiple bioinformatics platforms and web resources, which demonstrated that the SYK gene can be a potential biomarker for CRC. In this study, aromatic phytochemicals, such as kaempferol and glabridin that target the macromolecule (SYK kinase), showed higher stability than the controls, and we have estimated that these bioactive potential phytochemicals might be a useful option for CRC patients after the clinical trial. Conclusions: Our onco-informatics investigation suggests that the SYK gene can be a potential prognostic biomarker of CRC. On the contrary, SYK kinase would be a major target, and all selected compounds were validated against the protein using in-silico drug design approaches. Here, more in vitro and in vivo analysis is required for targeting SYK protein in CRC.

show abstract

Comprehensive analysis of Syk gene methylation in colorectal cancer

Zhu

Liu

et al. 2021

Immunity Inflam & Disease

Self Cite

View full text Add to dashboard Cite

Background: Metastasis of colorectal cancer (CRC) extremely affects the prognosis of CRC patients. Recently, the genetic methylation has been shown to associate with tumor metastasis. This research aimed to explore the Syk gene, which is frequently hypermethylated in different cancers, and its impact on the metastasis of CRC cells. Methods: We employed the UALCAN database for the detection of the methylation levels of Syk in different cancers. CIBERSORT, TIMER and TISIDB tools were employed to analyze the association of Syk expression with immune features of CRC. Treatment with decitabine has been noted to restore the expression of Syk in CRC cells. The invasion and migration abilities of CRC cell lines were determined using transwell and wound healing assays. The correlation between Syk and c‐Myc was established using the GEPIA2 database and Western blot assays. Results: Our results, based on UALCAN, revealed that the methylation level of Syk was altered in diverse cancers including colon adenocarcinoma. We found that expression profile and methylation level of Syk was correlated with immune features of colon adenocarcinoma. Decitabine can restore the expression of Syk in HCT116 and SW480 cells, hence affecting their migration and invasion. Results from GEPIA2 showed that Syk expression was correlated with c‐Myc, while Western blotting analysis revealed a negative association between the expression level of Syk and c‐Myc. Conclusions: This study demonstrates that the expression of Syk could be restored by decitabine in colorectal cancer, thus affecting the migration and invasion abilities of CRC cells.

show abstract

Comprehensive analysis of Syk gene methylation in colorectal cancer

Cited by 5 publications

References 36 publications

Molecular Characterization, Tumor Microenvironment Association, and Drug Susceptibility of DNA Methylation-Driven Genes in Renal Cell Carcinoma

Molecular Characterization, Tumor Microenvironment Association, and Drug Susceptibility of DNA Methylation-Driven Genes in Renal Cell Carcinoma

Analysis of SYK Gene as a Prognostic Biomarker and Suggested Potential Bioactive Phytochemicals as an Alternative Therapeutic Option for Colorectal Cancer: An In-Silico Pharmaco-Informatics Investigation

Comprehensive analysis of Syk gene methylation in colorectal cancer

Contact Info

Product

Resources

About