Downstream targets of GWAS-detected genes for breast, lung, and prostate and colon cancer converge to G1/S transition pathway

Gorlova, Olga Y.; Demidenko, Eugene; Amos, Christopher I.; Gorlov, Ivan P.

doi:10.1093/hmg/ddx050

Cited by 4 publications

(3 citation statements)

References 40 publications

(35 reference statements)

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“…In GSEA analysis, several pathways corresponding to SLC35A3 overexpression phenotype were signi cantly rich, including starch and sucrose metabolism pathway, cell cycle, DNA double strand break repair, base excision repair, epigenetic regulation of gene expression, and histone arginine methylation. These pathways are closely related to energy metabolism, cell proliferation, DNA damage repair, genome stability maintenance and epigenetic regulation of gene expression in CRC [51][52][53][54]. In addition, WNT signaling pathway, cancer pathway and multiple cancer invasive markers are signi cantly enriched in the low expression phenotype of SLC35A3, which indicates that SLC35A3 may play a role in regulating cancer signaling pathway, carcinogenesis and invasion in CRC.…”

Section: Discussionmentioning

confidence: 99%

Colorectal cancer with low SLC35A3 is associated with immune infiltrates and poor prognosis

Lü

Sun

Tang

et al. 2023

Preprint

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The expression level of SLC35A3 is related to the prognosis of many cancers, but its role in colorectal cancer (CRC) is still unknown. The purpose of our research is to clarify the role of SLC35A3 in the CRC. The expression level of SLC35A3 in CRC was evaluated by Tumor Immune Estimate Resource (TIMER), The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA) and qRT-PCR experiment. TCGA data set was used to analyze the diagnostic and prognostic value of SLC35A3 in CRC. An overall survival model was constructed and validated based on the expression level of SLC35A3 and the results of multivariate analysis. cBioPortal tool is used to analyze SLC35A3 mutation in CRC, and UALCAN tool was used to analyze the promoter methylation level of SLC35A3 in CRC. In addition, the role of SLC35A3 in the CRC was determined by GO analysis, KEGG analysis, gene set enrichment analysis (GSEA), immune infiltration analysis and correlation analysis of immune checkpoints. Compared with adjacent normal tissues of CRC and colon epithelial cells , the expression of SLC35A3 in CRC tissues and CRC cell lines decreased. The low expression of SLC35A3 is related to N stage, pathological stage and lymph infiltration, and is not conducive to overall survival (OS) and disease specific survival (DSS). According to Receiver Operating Characteristic (ROC) analysis, SLC35A3 could be an important diagnostic biomarker for patients with CRC. The nomograph based on SLC35A3 is a model superior to a single prognostic factor. SLC35A3 has multiple types mutations in CRC, and its promoter methylation level is significantly reduced. GO and KEGG analysis display the SLC35A3 may involved in the transmembrane transporter activity, cell communication and the interaction of neural active ligand receptors. GSEA disclosed that SLC35A3 may participate in energy metabolism, DNA repair, cancer pathway. In addition, SLC35A3 is closely related to a variety of immune cell infiltration and immune checkpoint expression. The results of this study indicate that the decreased expression of SLC35A3 is closely related to poor prognosis of CRC and immune cell infiltration. SLC35A3 is a promising independent prognostic biomarker and a potential therapeutic target for CRC.

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Section: Discussionmentioning

confidence: 99%

Colorectal cancer with low SLC35A3 is associated with immune infiltrates and poor prognosis

Lü

Sun

Tang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…In the GSEA analysis, several pathways corresponding to the overexpression phenotype of SLC35A3 were highly enriched, including starch and sucrose metabolism, cell cycle, DNA double-strand break repair, base excision repair, epigenetic regulation of gene expression, and histone arginine methylation. These pathways are closely related to energy metabolism of CRC, cell proliferation, DNA damage repair, maintenance of genomic stability, and epigenetic regulation of gene expression [62][63][64][65] . Additionally, in the low-expression phenotype of SLC35A3, WNT signaling pathway, cancer pathways, and various invasive markers of cancer were significantly enriched, suggesting that SLC35A3 may play a role in regulating cancer signaling pathways, the occurrence and invasion of CRC.…”

Section: Discussionmentioning

confidence: 99%

Colorectal cancer with low SLC35A3 is associated with immune infiltrates and poor prognosis

Lu,

Sun,

Tang

et al. 2024

Sci Rep

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The expression level of SLC35A3 is associated with the prognosis of many cancers, but its role in colorectal cancer (CRC) is unclear. The purpose of our study was to elucidate the role of SLC35A3 in CRC. The expression levels of SLC35A3 in CRC were evaluated through tumor immune resource assessment (TIMER), The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), International Cancer Genome Consortium (ICGC), Human Protein Atlas (HPA), qRT-PCR, and immunohistochemical evaluation. TCGA, GEO, and ICGC databases were used to analyze the diagnostic and prognostic value of SLC35A3 in CRC. A overall survival (OS) model was constructed and validated based on the expression level of SLC35A3 and multivariable analysis results. The cBioPortal tool was used to analyze SLC35A3 mutation in CRC. The UALCAN tool was used to analyze the promoter methylation level of SLC35A3 in colorectal cancer. In addition, the role of SLC35A3 in CRC was determined through GO analysis, KEGG analysis, gene set enrichment analysis (GSEA), immune infiltration analysis, and immune checkpoint correlation analysis. In vitro experiments validated the function of SLC35A3 in colorectal cancer cells. Compared with adjacent normal tissues and colonic epithelial cells, the expression of SLC35A3 was decreased in CRC tissues and CRC cell lines. Low expression of SLC35A3 was associated with N stage, pathological stage, and lymphatic infiltration, and it was unfavorable for OS, disease-specific survival (DSS), recurrence-free survival (RFS), and post-progression survival (PPS). According to the Receiver Operating Characteristic (ROC) analysis, SLC35A3 is a potential important diagnostic biomarker for CRC patients. The nomograph based on the expression level of SLC35A3 showed a better predictive model for OS than single prognostic factors and TNM staging. SLC35A3 has multiple types of mutations in CRC, and its promoter methylation level is significantly decreased. GO and KEGG analysis indicated that SLC35A3 may be involved in transmembrane transport protein activity, cell communication, and interaction with neurotransmitter receptors. GSEA revealed that SLC35A3 may be involved in energy metabolism, DNA repair, and cancer pathways. In addition, SLC35A3 was closely related to immune cell infiltration and immune checkpoint expression. Immunohistochemistry confirmed the positive correlation between SLC35A3 and helper T cell infiltration. In vitro experiments showed that overexpression of SLC35A3 inhibited the proliferation and invasion capability of colorectal cancer cells and promoted apoptosis. The results of this study indicate that decreased expression of SLC35A3 is closely associated with poor prognosis and immune cell infiltration in colorectal cancer, and it can serve as a promising independent prognostic biomarker and potential therapeutic target.

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“…In nonfunctional pituitary adenomas (NFPA), the overexpression of CDK1 and CDC25A may have an important role in promoting pituitary tumors in the G2/M transition phase ( 19 ). It has been reported that cell proliferation in hepatocellular carcinoma, nasopharyngeal carcinoma, breast cancer and colorectal cancer can be inhibited by regulating the expression of genes that induce cell cycle arrest at the G1/S phase ( 20 – 22 ). Similarly, in LC, aberrant expression of the cell cycle regulation-related genes Cyclin D1, Cyclin E, Cyclin A, CDC25A and CDK4 could facilitate the transcription and expression of genes that are associated with cell cycle progression ( 23 ).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of differential expression profiles reveals potential biomarkers associated with the cell cycle and regulated by p53 in human small cell lung cancer

Wang

Zhang

et al. 2018

Exp Ther Med

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Small cell lung cancer (SCLC) is the subtype of lung cancer with the highest degree of malignancy and the lowest degree of differentiation. The purpose of this study was to investigate the molecular mechanisms of SCLC using bioinformatics analysis, and to provide new ideas for the early diagnosis and targeted therapy of SCLC. Microarray data were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) in SCLC were compared with the normal lung samples and identified. Gene Ontology (GO) function and pathway analysis of DEGs was performed through the DAVID database. Furthermore, microarray data was analyzed by using the clustering analysis tool GoMiner. Protein-protein interaction (PPI) networks of DEGs were constructed using the STRING online database. Protein expression was determined from the Human Protein Atlas, and SCLC gene expression was determined using Oncomine. In total, 153 DEGs were obtained. Functional enrichment analysis suggested that the majority of DEGs were associated with the cell cycle. CCNB1, CCNB2, MAD2L1 and CDK1 were identified to contribute to the progression of SCLC through combined use of GO, Kyoto Encyclopedia of Genes and Genomes enrichment analysis and a PPI network. mRNA and protein expression were also validated in an integrative database. The present study indicated that the formation of SCLC may be associated with cell cycle regulation. In addition, the four crucial genes CCNB1, CCNB2, MAD2L1 and CDK1, which are downstream of p53, may have important roles in the occurrence and progression of SCLC, and thus may be promising potential biomarkers and therapeutic targets.

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Downstream targets of GWAS-detected genes for breast, lung, and prostate and colon cancer converge to G1/S transition pathway

Cited by 4 publications

References 40 publications

Colorectal cancer with low SLC35A3 is associated with immune infiltrates and poor prognosis

Colorectal cancer with low SLC35A3 is associated with immune infiltrates and poor prognosis

Colorectal cancer with low SLC35A3 is associated with immune infiltrates and poor prognosis

Comprehensive analysis of differential expression profiles reveals potential biomarkers associated with the cell cycle and regulated by p53 in human small cell lung cancer

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