Integrative bioinformatics analysis of high-throughput sequencing and in vitro functional analysis leads to uncovering key hub genes in esophageal squamous cell carcinoma DOI Creative Commons
Feng Shen, Xing Liu,

Fengjiao Ding

et al.

Hereditas, Journal Year: 2025, Volume and Issue: 162(1)

Published: March 14, 2025

Abstract Background Esophageal squamous cell carcinoma (ESCA) is a type of cancer that starts in the cells lining esophagus, tube connecting throat to stomach. It known for its aggressive nature and poor prognosis. Understanding key factors drive this crucial developing better diagnostic tools treatments. Methods Gene expression profiles ESCA were analyzed using Expression Omnibus (GEO) datasets (GSE23400, GSE29001, GSE92396, GSE1420) from GEO database. Differentially expressed genes (DEGs) identified limma package, protein-protein interaction (PPI) network was constructed STRING Hub based on degree method. Further validation performed through reverse transcription quantitative PCR (RT-qPCR), mutational copy number variation (CNV) analysis via cBioPortal database, promoter methylation OncoDB GSCA databases, survival analysis, immune infiltration functional assays, including knockdown genes. Results We four hub genes, COL3A1, COL4A1, COL5A2, CXCL8 play significant roles ESCA. These highly tissues lines, with levels significantly (p-value < 0.001) elevated compared normal controls. Receiver operating characteristic (ROC) curve revealed exceptional performance all area under (AUC) values 1.0, indicating perfect sensitivity specificity distinguishing Mutational COL3A1 altered 67% samples, primarily missense mutations, while COL5A2 exhibited alterations 50% splice site mutations. Additionally, gene amplification patterns observed further validating their oncogenic potential progression. A 0.05) hypomethylation detected these suggesting regulatory role expression. Functional assays demonstrated knocking down COL4A1 led decreased proliferation, colony formation, migration, critical tumor involved pathways related extracellular matrix system modulation. Conclusion are development progression, particularly remodeling matrix, modulating system, promoting metastasis. findings suggest could serve as biomarkers diagnosing targets future therapies. Future research should focus vivo clinical testing assess therapeutic targeting treatment.

Language: Английский

ECM, integrins, and DDRs: A nexus of cancer progression, therapy, and future directions DOI
M A Azim, Julie S. Di Martino

Matrix Biology, Journal Year: 2025, Volume and Issue: 138, P. 27 - 43

Published: April 12, 2025

Language: Английский

Citations

0
Integrative bioinformatics analysis of high-throughput sequencing and in vitro functional analysis leads to uncovering key hub genes in esophageal squamous cell carcinoma DOI Creative Commons
Feng Shen, Xing Liu,

Fengjiao Ding

et al.

Hereditas, Journal Year: 2025, Volume and Issue: 162(1)

Published: March 14, 2025

Abstract Background Esophageal squamous cell carcinoma (ESCA) is a type of cancer that starts in the cells lining esophagus, tube connecting throat to stomach. It known for its aggressive nature and poor prognosis. Understanding key factors drive this crucial developing better diagnostic tools treatments. Methods Gene expression profiles ESCA were analyzed using Expression Omnibus (GEO) datasets (GSE23400, GSE29001, GSE92396, GSE1420) from GEO database. Differentially expressed genes (DEGs) identified limma package, protein-protein interaction (PPI) network was constructed STRING Hub based on degree method. Further validation performed through reverse transcription quantitative PCR (RT-qPCR), mutational copy number variation (CNV) analysis via cBioPortal database, promoter methylation OncoDB GSCA databases, survival analysis, immune infiltration functional assays, including knockdown genes. Results We four hub genes, COL3A1, COL4A1, COL5A2, CXCL8 play significant roles ESCA. These highly tissues lines, with levels significantly (p-value < 0.001) elevated compared normal controls. Receiver operating characteristic (ROC) curve revealed exceptional performance all area under (AUC) values 1.0, indicating perfect sensitivity specificity distinguishing Mutational COL3A1 altered 67% samples, primarily missense mutations, while COL5A2 exhibited alterations 50% splice site mutations. Additionally, gene amplification patterns observed further validating their oncogenic potential progression. A 0.05) hypomethylation detected these suggesting regulatory role expression. Functional assays demonstrated knocking down COL4A1 led decreased proliferation, colony formation, migration, critical tumor involved pathways related extracellular matrix system modulation. Conclusion are development progression, particularly remodeling matrix, modulating system, promoting metastasis. findings suggest could serve as biomarkers diagnosing targets future therapies. Future research should focus vivo clinical testing assess therapeutic targeting treatment.

Language: Английский

Citations

0