Dipeptidase 1 (DPEP1) is a marker for the transition from low-grade to high-grade intraepithelial neoplasia and an adverse prognostic factor in colorectal cancer

Eisenach, Patricia A.; Soeth, Edlyn; Röder, Christian; Klöppel, Günter; Tepel, Jürgen; Kalthoff, Holger; Sipos, Bence

doi:10.1038/bjc.2013.363

Cited by 44 publications

(44 citation statements)

References 27 publications

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“…Furthermore, in the IHC staining analysis, upregulated DPEP1 expression was associated with poorer tumor histology. These findings were consistent with previous studies demonstrating that DPEP1 is highly expressed in CRC compared with matched normal mucosa, indicating a significant role of DPEP1 in CRC development (16,17). While the current results indicate the oncogenic role of DPEP1 in CRC, no significant associations between DPEP1 expression levels and patient prognosis, as well as EMT status, were observed in the current cohort.…”

Section: Discussionsupporting

confidence: 92%

“…Consistent with this, DPEP1 is considered to be a tumor suppressor gene in breast cancer and pancreatic ductal adenocarcinoma (14,15). However, DPEP1 is upregulated in CRC and its high expression level is associated with poorer patient survival (16). Furthermore, a recent report demonstrated that DPEP1 is highly expressed in CRC and promotes metastasis via regulation of E-cadherin expression levels (17).…”

Section: Introductionmentioning

confidence: 76%

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Clinicopathological examination of dipeptidaseï¿½1 expression in colorectal cancer

et al. 2017

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Abstract. Dipeptidase 1 (DPEP1) is a zinc-dependent metalloproteinase that is fundamental in glutathione and leukotriene metabolism. DPEP1 was initially considered as a tumor suppressor gene in Wilms' tumor and breast cancer. However, it has been reported that DPEP1 is upregulated in colorectal cancers (CRCs) and high DPEP1 expression levels are associated with poorer patient survival. The role of DPEP1 genes in CRC, as well as their expression, requires investigation. Therefore, the present study investigated DPEP1 expression using reverse transcription-quantitative polymerase chain reaction or immunohistochemistry on surgically resected samples from CRC cases, and further examined the biological significance of DPEP1 by comparing the expression of the epithelial to mesenchymal transition (EMT) markers, including epithelial cadherin and Vimentin to clarify the function of DPEP1 in CRC, particularly in metastasis. The level of DPEP1 expression was identified to be significantly increased in tumorous tissue samples compared with that in non-tumorous tissue samples. In addition, increased DPEP1 mRNA expression levels were associated with positive lymph node metastasis in the included cohort. However, no positive correlations were observed between DPEP1 and EMT markers in the cohort. The results indiciates that further investigations into the upregulation of DPEP1 in colorectal carcinogenesis and the role of therapeutic or prognostic biomarkers are required.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 76%

Clinicopathological examination of dipeptidaseï¿½1 expression in colorectal cancer

et al. 2017

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“…Membrane-bound DPEP1 is a zinc-dependent metalloproteinase that has been shown to process a plethora of peptides and antibiotics, as well as to be involved in the glutathione and leukotriene metabolism3132. DPEP1 has been identified as a prognostic gene of colorectal cancer33. In the current study, we showed that DPEP1 was overexpressed in CRC, and knockdown of DPEP1 in SW480 and HCT116 cells significantly increased cell apoptosis and attenuated cell proliferation and invasion.…”

Section: Discussionmentioning

confidence: 51%

Comprehensive Proteomic Characterization of the Human Colorectal Carcinoma Reveals Signature Proteins and Perturbed Pathways

Hao

Zhi

Wang

et al. 2017

Sci Rep

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The global change in protein abundance in colorectal cancer (CRC) and its contribution to tumorigenesis have not been comprehensively analyzed. In this study, we conducted a comprehensive proteomic analysis of paired tumors and adjacent tissues (AT) using high-resolution Fourier-transform mass spectrometry and a novel algorithm of quantitative pathway analysis. 12380 proteins were identified and 740 proteins that presented a 4-fold change were considered a CRC proteomic signature. A significant pattern of changes in protein abundance was uncovered which consisted of an imbalance in protein abundance of inhibitory and activating regulators in key signal pathways, a significant elevation of proteins in chromatin modification, gene expression and DNA replication and damage repair, and a decreased expression of proteins responsible for core extracellular matrix architectures. Specifically, based on the relative abundance, we identified a panel of 11 proteins to distinguish CRC from AT. The protein that showed the greatest degree of overexpression in CRC compared to AT was Dipeptidase 1 (DPEP1). Knockdown of DPEP1 in SW480 and HCT116 cells significantly increased cell apoptosis and attenuated cell proliferation and invasion. Together, our results show one of largest dataset in CRC proteomic research and provide a molecular link from genomic abnormalities to the tumor phenotype.

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“…The up-regulation of DPEP1 mRNA in G8D was confirmed by qRT-PCR ( Figure 4C). Because DPEP1 expression is higher in paired tumors than in adjacent tissues 20 and in tumor tissues than in normal mucosa 21,22 , we further studied the role of this gene in sphere formation. Two different lentiviral small hairpin RNAs were used to stably knockdown DPEP1 in G8D.…”

Section: Rna Sequencing Identifies Dpep1 As a Highly Expressed Gene Imentioning

confidence: 99%

Selection of a Malignant Subpopulation from a Colorectal Cancer Cell Line

Lai

Chen

Feng

et al. 2019

Preprint

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Colorectal cancer (CRC) is a leading cause of death from cancer worldwide. Thus, there is an emerging need for new experimental models that allow identification and validation of biomarkers for CRC-specific progression. In this study, we propose a repeated sphere-forming assay as a strategy to select a malignant subpopulation from a CRC line, HCT116. We validated our assay by confirming that three canonical stemness markers, Nanog, Oct4, and Lgr5, were up-regulated in the sphere state at every generation of the selection assay. The resulting line, after eight rounds of selection, exhibited an increased sphere-forming capacity in vitro and tumorgenicity in vivo. Furthermore, dipeptidase 1 (DPEP1) was identified as the major differentially expressed gene in the selected clone, and depletion of DPEP1 suppressed the elevated sphere-forming capacity in vitro and tumorgenicity in vivo. Overall, we have established an experimental strategy for the isolation of a malignant subpopulation from a CRC cell line. Results from our model also suggested that DPEP1 can serve as a promising prognostic biomarker for CRC.

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Dipeptidase 1 (DPEP1) is a marker for the transition from low-grade to high-grade intraepithelial neoplasia and an adverse prognostic factor in colorectal cancer

Cited by 44 publications

References 27 publications

Clinicopathological examination of dipeptidaseï¿½1 expression in colorectal cancer

Clinicopathological examination of dipeptidaseï¿½1 expression in colorectal cancer

Comprehensive Proteomic Characterization of the Human Colorectal Carcinoma Reveals Signature Proteins and Perturbed Pathways

Selection of a Malignant Subpopulation from a Colorectal Cancer Cell Line

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