FOXE1 and SYNE1 Genes Hypermethylation Panel as Promising Biomarker in Colitis-associated Colorectal Neoplasia

Papadia, Cinzia; Louwagie, Joost; Río, Paolo Del; Grooteclaes, Madeleine; Coruzzi, Alessandro; Montana, Chiara; Novelli, Marco; Bordi, Cesare; Angelis, Gian Luigi De’; Bassett, Paul; Bigley, Joseph; Warren, Bryan F.; Atkin, Wendy; Forbes, Alastair

doi:10.1097/01.mib.0000435443.07237.ed

Cited by 27 publications

(23 citation statements)

References 32 publications

(33 reference statements)

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“…Any particular genetic alteration that demonstrates a preferential or increased expression in dysplastic and neoplastic tissues might be thought of as a potential marker of cancer progression. Many markers have been evaluated in this way [25,26,27]. However, there is no consensus as to how these markers of cancer risk should be incorporated into the clinical management of patients with long-standing IBD [14,16,28,29].…”

Section: Molecular Mechanisms Of Ibd-associated Colon Carcinogenesismentioning

confidence: 99%

Colorectal Cancer in Patients with Inflammatory Bowel Disease: The True Impact of the Risk

Herszényi¹,

Barabás

Miheller³

et al. 2014

Dig Dis

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Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC). The association between IBD and CRC is well supported, but reported risk estimates vary widely. Although recent evidence from population-based studies reports a decline in risk, CRC accounts for 10-15% of all deaths in IBD. The potential causes of recent epidemiological trends and the real magnitude of risk of CRC in IBD are subjects of debate. The molecular pathway leading to CRC differs from the classic adenoma-to-CRC sequence. Chronic inflammation contributes to the development of low- and high-grade dysplasia which may further convert into CRC. Patients with a young age at onset, long-standing and extensive colitis with severe inflammatory burden, a family history of sporadic CRC, and concomitant primary sclerosing cholangitis are at greatest risk. The CRC risk in patients with colonic Crohn's disease is similar to that of ulcerative colitis. IBD-associated CRC can frequently be detected at late stages and at a younger age. The long-term prognosis of CRC may be poorer in patients with IBD than in those with sporadic CRC. Regular surveillance colonoscopies may permit earlier detection of CRC, with a corresponding improved prognosis. The interval between surveillance colonoscopies is dependent on each patient's personal risk profile.

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Section: Molecular Mechanisms Of Ibd-associated Colon Carcinogenesismentioning

confidence: 99%

Colorectal Cancer in Patients with Inflammatory Bowel Disease: The True Impact of the Risk

Herszényi¹,

Barabás

Miheller³

et al. 2014

Dig Dis

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“…FOXE1 and SYNE1 were identified as frequently methylated genes using a transcriptome-wide approach to identify genes that are transcriptionally silenced by methylation in colorectal cancer (32). In addition, methylation of SYNE1 and FOXE1 has been described in a small cohort of patients with colitis-associated colorectal neoplasia (33). …”

Section: Introductionmentioning

confidence: 99%

Spectrin Repeat Containing Nuclear Envelope 1 and Forkhead Box Protein E1 Are Promising Markers for the Detection of Colorectal Cancer in Blood

Melotte

Lentjes

et al. 2015

Cancer Prevention Research

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Identifying biomarkers in body fluids may improve the noninvasive detection of colorectal cancer. Previously, we identified N-Myc downstream-regulated gene 4 (NDRG4) and GATA binding protein 5 (GATA5) methylation as promising biomarkers for colorectal cancer in stool DNA. Here, we examined the utility of NDRG4, GATA5, and two additional markers [Forkhead box protein E1 (FOXE1) and spectrin repeat containing nuclear envelope 1 (SYNE1)] promoter methylation as biomarkers in plasma DNA. Quantitative methylation-specific PCR was performed on plasma DNA from 220 patients with colorectal cancer and 684 noncancer controls, divided in a training set and a test set. Receiver operating characteristic analysis was performed to measure the area under the curve of GATA5, NDRG4, SYNE1, and FOXE1 methylation. Functional assays were performed in SYNE1 and FOXE1 stably transfected cell lines. The sensitivity of NDRG4, GATA5, FOXE1, and SYNE1 methylation in all stages of colorectal cancer (154 cases, 444 controls) was 27% [95% confidence interval (CI), 20%–34%), 18% (95% CI, 12%–24%), 46% (95% CI, 38%– 54%), and 47% (95% CI, 39%–55%), with a specificity of 95% (95% CI, 93%–97%), 99% (95% CI, 98%–100%), 93% (95% CI, 91%–95%), and 96% (95% CI, 94%–98%), respectively. Combining SYNE1 and FOXE1, increased the sensitivity to 56% (95% CI, 48%–64%), while the specificity decreased to 90% (95% CI, 87%–93%) in the training set and to 58% sensitivity (95% CI, 46%–70%) and 91% specificity (95% CI, 80%–100%) in a test set (66 cases, 240 controls). SYNE1 overexpression showed no major differences in cell proliferation, migration, and invasion compared with controls. Overexpression of FOXE1 significantly decreased the number of colonies in SW480 and HCT116 cell lines. Overall, our data suggest that SYNE1 and FOXE1 are promising markers for colorectal cancer detection.

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“…A previous study demonstrated that APP expression levels correlated with the extent of disease and the prognosis in several forms of cancer (28). In addition, SYNE1 is a promising biomarker in colitis-associated colorectal cancer (29). As previously suggested, RTN4 contributes to the susceptibility of cervical squamous cell carcinoma (30).…”

Section: Discussionmentioning

confidence: 75%

Genome-wide analysis of androgen receptor binding sites in prostate cancer cells

Cheng

Pan

Duan

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The transformation of prostate cancer from an androgen-dependent state to an androgen-independent state is a lethal progression. Alterations in transcriptional programs are the basis of prostate cancer deterioration. The androgen receptor (AR), a member of the nuclear hormone receptor superfamily, mediates prostate cancer progression by functioning primarily through the ligand-activated transcription of target genes. Therefore, a detailed map of AR-regulated genes and AR genomic binding sites is required for hormone-naive and castration-resistant prostate cancer. Through the use of chromatin immunoprecipitation in combination with direct sequencing, 4,143 AR binding sites were defined in the LNCaP androgen-sensitive prostate cancer cell line. Using the same method, 2,380 AR binding regions were identified in the LNCaP-AI long-term androgen-deprived cell line. Approximately 8.5% (354/4,143) of the binding regions were mapped to within 2 kb of the transcription start site (TSS) in the LNCaP cells, while ~12.6% (299/2,380) were mapped to within 2 kb of the TSS in the LNCaP-AI cells. In total, the study mapped 2,796 genes in LNCaP cells and 1,854 genes in LNCaP-AI cells. The cell lines shared 789 mutual genes. In addition, gene ontology (GO) analysis of the genes revealed that there was a notable overlap between the GO terms in the LNCaP cells and LNCaP-AI cells. However, GO terms within the biological process domain that were only observed in the LNCaP-AI cells included the reproduction process, death, immune system process, multi-organism process, pigmentation and viral reproduction. The major genes in the different GO terms were TNFAIP8, RTN4, APP and SYNE1. Through analyzing the AR binding sites in the two cell types, the present study aimed to map potential AR-regulated genes, identify their associated transcription factors and provide a new perspective on the biological processes in the development of prostate cancer. The results provided a valuable data set that furthered the understanding of the genome-wide analysis of AR binding sites in prostate cancer cells, which may be exploited for the development of novel prostate cancer therapeutic strategies.

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FOXE1 and SYNE1 Genes Hypermethylation Panel as Promising Biomarker in Colitis-associated Colorectal Neoplasia

Abstract: FOXE1 and SYNE1 hypermethylation markers demonstrated significantly increased expression in neoplastic tissue. Promoter methylation analysis of these genes might be a useful marker of neoplasia in long-standing IBD.

Cited by 27 publications

References 32 publications

Colorectal Cancer in Patients with Inflammatory Bowel Disease: The True Impact of the Risk

Colorectal Cancer in Patients with Inflammatory Bowel Disease: The True Impact of the Risk

Spectrin Repeat Containing Nuclear Envelope 1 and Forkhead Box Protein E1 Are Promising Markers for the Detection of Colorectal Cancer in Blood

Genome-wide analysis of androgen receptor binding sites in prostate cancer cells

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