Microarray analysis of copy-number variations and gene expression profiles in prostate cancer

Jin, Xin; Li, Hongyan; Wang, Kai-Chen; Gao, Ji; Song, Lide; Lv, Yanting

doi:10.1097/md.0000000000007264

Cited by 7 publications

(5 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Li reported that FAT4 could act as a mediator in the down-regulation of lncRNA RNAZFHX4-AS1, so as to inhibit the migration and invasion of breast cancer ( 11 ). Han investigated the pathogenesis of prostate cancer, and pointed out that the knockdown of FAT4 resulted in a more severe condition of prostate cancer ( 12 ). Epithelial-mesenchymal transition (EMT) process refers to a physiological process associated with tumor cell migration and invasion that affect greatly tumor metastasis and development ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

Up-regulation of FAT4 enhances the chemosensitivity of colorectal cancer cells treated by 5-FU

Li¹,

Zhou²,

Fang³

et al. 2020

Transl Cancer Res TCR

View full text Add to dashboard Cite

Background Colorectal cancer (CRC) has high mortality, and 5-fluorouracil (5-FU) is a common clinical chemotherapeutic drug. The current study aimed to investigate the role of FAT4 in chemosensitivity of CRC cells treated by 5-FU. Methods The immunohistochemistry and qRT-PCR was conducted to measure the FAT4 expression in CRC and adjacent tissues. The FAT4 expression was determined by qRT-PCR and Western blot, comparison of FAT expression between normal and several CRC cell lines was then made, so as to identify cell lines with the highest (LS174T) and the lowest (SW-620) expressions of FAT4 . The effects of 5-FU stimulation at various doses on cell viability were determined by CCK-8, and the level of FAT4 was also measured. After FAT4 knockdown in LS174T or FAT4 overexpression in SW-620 with or without pretreatment of 5-FU (30 µg/mL), cell growth, colony formation, cell migration and invasion, angiogenesis were determined by flow cytometry, wound-healing, transwell assay and tube formation assay, respectively. The expression levels of epithelial-mesenchymal transition (EMT) markers were detected by qRT-PCR and Western blot. Results FAT4 was down-regulated in CRC tissues and cells, cell viability of CRC cells was decreased. The level of FAT4 was increased with the increase of 5-FU concentrations. Moreover, 5-FU stimulation increased FAT4 expression, and reduced cell proliferation, migration, invasion, angiogenesis and cell EMT process, furthermore, such effects of 5-FU stimulation could be enhanced by FAT4 overexpression but reversed by FAT4 knockdown. Conclusions Upregulation of FAT4 could increase the sensitivity of CRC cells to 5-FU.

show abstract

Section: Introductionmentioning

confidence: 99%

Up-regulation of FAT4 enhances the chemosensitivity of colorectal cancer cells treated by 5-FU

Li¹,

Zhou²,

Fang³

et al. 2020

Transl Cancer Res TCR

View full text Add to dashboard Cite

show abstract

“…Among these four genes, MARCKS had the highest CNV loss frequency. CNV mutation burden affects gene expression level or activity, thereby influencing genetic modulation and causing PRAD progression [ 63 , 64 ]. We further clarified the differentiation ability of APPCAF signature genes for prostate cancer via NMF clustering, which suggests that patients in APPRG Cluster C2 are associated with poorer clinical outcomes, and we discovered that prostate cancer samples with varying APPRG expression levels were significantly correlated with various pathways.…”

Section: Discussionmentioning

confidence: 99%

Integrating single-cell and bulk RNA sequencing data unveils antigen presentation and process-related CAFS and establishes a predictive signature in prostate cancer

Wang,

Li,

Xie

et al. 2024

J Transl Med

View full text Add to dashboard Cite

Background Cancer-associated fibroblasts (CAFs) are heterogeneous and can influence the progression of prostate cancer in multiple ways; however, their capacity to present and process antigens in PRAD has not been investigated. In this study, antigen presentation and process-related CAFs (APPCAFs) were identified using bioinformatics, and the clinical implications of APPCAF-related signatures in PRAD were investigated. Methods SMART technology was used to sequence the transcriptome of primary CAFs isolated from patients undergoing different treatments. Differential expression gene (DEG) screening was conducted. A CD4 + T-cell early activation assay was used to assess the activation degree of CD4 + T cells. The datasets of PRAD were obtained from The Cancer Genome Atlas (TCGA) database and NCBI Gene Expression Omnibus (GEO), and the list of 431 antigen presentation and process-related genes was obtained from the InnateDB database. Subsequently, APP-related CAFs were identified by nonnegative matrix factorization (NMF) based on a single-cell seq (scRNA) matrix. GSVA functional enrichment analyses were performed to depict the biological functions. A risk signature based on APPCAF-related genes (APPCAFRS) was developed by least absolute shrinkage and selection operator (LASSO) regression analysis, and the independence of the risk score as a prognostic factor was evaluated by univariate and multivariate Cox regression analyses. Furthermore, a biochemical recurrence-free survival (BCRFS)-related nomogram was established, and immune-related characteristics were assessed using the ssGSEA function. The immune treatment response in PRAD was further analyzed by the Tumor Immune Dysfunction and Exclusion (TIDE) tool. The expression levels of hub genes in APPCAFRS were verified in cell models. Results There were 134 upregulated and 147 downregulated genes, totaling 281 differentially expressed genes among the primary CAFs. The functions and pathways of 147 downregulated DEGs were significantly enriched in antigen processing and presentation processes, MHC class II protein complex and transport vesicle, MHC class II protein complex binding, and intestinal immune network for IgA production. Androgen withdrawal diminished the activation effect of CAFs on T cells. NMF clustering of CAFs was performed by APPRGs, and pseudotime analysis yielded the antigen presentation and process-related CAF subtype CTSK + MRC2 + CAF-C1. CTSK + MRC2 + CAF-C1 cells exhibited ligand‒receptor connections with epithelial cells and T cells. Additionally, we found a strong association between CTSK + MRC2 + CAF-C1 cells and inflammatory CAFs. Through differential gene expression analysis of the CTSK + MRC2 + CAF-C1 and NoneAPP-CAF-C2 subgroups, 55 significant DEGs were identified, namely, APPCAFRGs. Based on the expression profiles of APPCAFRGs, we divided the TCGA-PRAD cohort into two clusters using NMF consistent cluster analysis, with the genetic coefficient serving as the evaluation index. Four APPCAFRGs, THBS2, DPT, COL5A1, and MARCKS, were used to develop a prognostic signature capable of predicting BCR occurrence in PRAD patients. Subsequently, a nomogram with stability and accuracy in predicting BCR was constructed based on Gleason grade (p = n.s.), PSA (p < 0.001), T stage (p < 0.05), and risk score (p < 0.01). The analysis of immune infiltration showed a positive correlation between the abundance of resting memory CD4 + T cells, M1 macrophages, resting dendritic cells, and the risk score. In addition, the mRNA expression levels of THBS2, DPT, COL5A1, and MARCKS in the cell models were consistent with the results of the bioinformatics analysis. Conclusions APPCAFRS based on four potential APPCAFRGs was developed, and their interaction with the immune microenvironment may play a crucial role in the progression to castration resistance of PRAD. This novel approach provides valuable insights into the pathogenesis of PRAD and offers unexplored targets for future research.

show abstract

“…It is estimated that up to 60% of the human genome may contain structural variants in the general population, which typically range in size from 100 bp to 50 kb (Escaramis, Docampo, & Rabionet, 2015), and clinical interpretation of these aberrations when identified by CMA testing is facilitated by professional medical genetics practice guidelines (South et al, 2013). Larger gene-dense aberrations are more likely to result in penetrant syndromic phenotypes; however, some smaller CNVs have increasingly been implicated as susceptibility alleles for several phenotypes, including neurodegenerative disorders, cancer, autism, and psychiatric diseases (Cook & Scherer, 2008;Gonzalez et al, 2005;Han et al, 2017;Nishioka et al, 2006;Rovelet-Lecrux et al, 2006;Sebat et al, 2007). CNVs can influence these human traits by altering the copy number of dosage-sensitive genes (Douglas et al, 2005;Roa, Garcia, & Lupski, 1991) and/or modulating local gene expression (Cahan, Li, Izumi, & Graubert, 2009;Henrichsen, Chaignat, & Reymond, 2009).…”

Section: Cyp2c Deletion and Duplication Frequencies And Allele Nomementioning

confidence: 99%

Structural variation at the CYP2C locus: Characterization of deletion and duplication alleles

Botton

Zhao

et al. 2019

Human Mutation

View full text Add to dashboard Cite

The human CYP2C locus harbors the polymorphic CYP2C18, CYP2C19, CYP2C9, and CYP2C8 genes, and of these, CYP2C19 and CYP2C9 are directly involved in the metabolism of ~15% of all medications. All variant CYP2C19 and CYP2C9 star (*) allele haplotypes currently cataloged by the Pharmacogene Variation (PharmVar) Consortium are defined by sequence variants. To determine if structural variation also occurs at the CYP2C locus, the 10q23.33 region was interrogated across deidentified clinical chromosomal microarray (CMA) data from 20,642 patients tested at two academic medical centers. Fourteen copy number variants that affected the coding region of CYP2C genes were detected in the clinical CMA cohorts, which ranged in size from 39.2 to 1,043.3 kb. Selected deletions and duplications were confirmed by MLPA or ddPCR. Analysis of the clinical CMA and an additional 78,839 cases from the Database of Genomic Variants (DGV) and ClinGen (total n = 99,481) indicated that the carrier frequency of a CYP2C structural variant is ~1 in 1,000, with ~1 in 2,000 being a CYP2C19 full gene or partial‐gene deletion carrier, designated by PharmVar as CYP2C19*36 and *37, respectively. Although these structural variants are rare in the general population, their detection will likely improve metabolizer phenotype prediction when interrogated for research and/or clinical testing.

show abstract

Microarray analysis of copy-number variations and gene expression profiles in prostate cancer

Abstract: Supplemental Digital Content is available in the text

Cited by 7 publications

References 44 publications

Up-regulation of FAT4 enhances the chemosensitivity of colorectal cancer cells treated by 5-FU

Up-regulation of FAT4 enhances the chemosensitivity of colorectal cancer cells treated by 5-FU

Integrating single-cell and bulk RNA sequencing data unveils antigen presentation and process-related CAFS and establishes a predictive signature in prostate cancer

Structural variation at the CYP2C locus: Characterization of deletion and duplication alleles

Contact Info

Product

Resources

About