Ensemble of Gene Signatures Identifies Novel Biomarkers in Colorectal Cancer Activated through PPARγ and TNFα Signaling

Pagnotta, Stefano Maria; Laudanna, Carmelo; Pancione, Massimo; Sabatino, Lina; Votino, Carolina; Remo, Andrea; Cerulo, Luigi; Zoppoli, Pietro; Manfrin, Erminia; Colantuoni, Vittorio; Ceccarelli, Michele

doi:10.1371/journal.pone.0072638

Cited by 35 publications

(22 citation statements)

References 37 publications

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“…Moreover, in breast and prostate cancers, AKT can also be activated by other RTKs through TRAF6-mediated signaling (8,9). In this study, we describe a novel function of DCBLD2, an orphan membrane receptor that has an unclear role in human cancers (15)(16)(17)39), in mediating EGFR/AKT-driven tumorigenesis. We show that DCBLD2 is expressed at high levels in clinical samples of GBMs and HNCs.…”

Section: Discussionmentioning

confidence: 89%

EGFR phosphorylation of DCBLD2 recruits TRAF6 and stimulates AKT-promoted tumorigenesis

Feng¹,

López²,

Kim³

et al. 2014

J. Clin. Invest.

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BACKGROUND: Oncogenic EGFR-Akt signaling is aberrantly activated in human glioblastomas. Discoid, CUC and LCCL domain containing protein 2 (DCBLD2, also known as CLCP1 and ESDN) is a neuropilin-like membrane protein that is up-regulated in vascular injury and metastatic lung cancers. However, the role of DCBLD2 in cancer is unclear. METHODS: We examined the expression of DCBLD2 in TCGA and other data bases of clinical glioma

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Section: Discussionmentioning

confidence: 89%

EGFR phosphorylation of DCBLD2 recruits TRAF6 and stimulates AKT-promoted tumorigenesis

Feng¹,

López²,

Kim³

et al. 2014

J. Clin. Invest.

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“…However, it is of note that our results should be considered exploratory because of the limited sample size of the study. We and others have identified that high expression of CD73 in tumor cells can be used as an independent prognostic biomarker for human CRC [19,22,23]. Thus, the tumoral expression levels of CD73 and CD39 were combined to evaluate the prognostic value in the current study.…”

Section: Discussionmentioning

confidence: 99%

High expression of CD39/ENTPD1 in malignant epithelial cells of human rectal adenocarcinoma

Zhang

Cheng

et al. 2015

Tumor Biol.

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The ectonucleotidase CD39 is pivotal in the conversion of immunostimulatory adenosine triphosphate (ATP) into immunosuppressive adenosine which potently inhibits host immune responses against cancer. This study investigated the expression level and prognostic significance of CD39 in human rectal adenocarcinoma. Our data demonstrated that CD39 staining strongly marked malignant epithelial cells where the protein and messenger RNA (mRNA) expression levels of CD39 were significantly increased compared with paracancerous controls. In addition to primary tumors, CD39 was also abundantly expressed in liver metastases and tumor-draining lymph nodes from metastatic rectal adenocarcinoma. Although patients with higher CD39 density in tumor cells were more likely to have favorable characteristics (early TNM and N stages) and overall survival, the singular parameter cannot be used as an independent factor for predicting patients' prognosis. Intriguingly, combined analysis of CD39 and CD73 expression was more efficient to foretell patient's outcome where patients with increased CD73 but decreased CD39 levels displayed a worst prognosis. Taken together, the current study revealed that malignant epithelial cells of human rectal adenocarcinoma strongly express CD39 that may play a potential role in the tumor invasion and metastasis. Although high expression of CD39 in tumor cells is correlated with favorable clinical outcome, the combination of CD39 and CD73 expression may have a better prognostic value.

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“…DCBLD2 and GSDMD have considerable tumor-specific effects, but their roles.in PDAC development remain unclear. DCBLD2 is overexpressed in glioblastoma, colorectal cancer, and lung cancer [39][40][41], and it is strongly associated with tumor migration and invasion. GSDMD plays an important role in the regulation of pyroptosis and sensitivity to cancer therapy [42].…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a cancer stem cell-related signature for prognostic prediction in pancreatic ductal adenocarcinoma

Feng

Shi

et al. 2020

Preprint

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Background Cancer stem cells (CSCs) are crucial to malignant behavior and poor prognosis of pancreatic ductal adenocarcinoma (PDAC). In recent years, CSC biology has been widely studied, but practical prognostic signatures based on CSC-related genes have not been established and reported in PDAC. Methods This signature was developed and validated in seven independent PDAC datasets. MTAB-6134 cohort was used as training set, while one Chinese local cohort and five other public cohorts were used for external validation. CSC-related genes with credible prognostic roles were selected to form the signature, and its predictive performance was evaluated by Kaplan-Meier survival, receiver operating characteristic (ROC), and calibration curves. Correlation analysis was employed to clarify the potential biological characteristics. Results A robust signature comprising DCBLD2, GSDMD, PMAIP1, and PLOD2 was developed. It could classify patients into high-risk and low-risk groups, and high risk patients had significantly shorter overall survival (OS) and disease-free survival (DFS) compared with low risk patients. Calibration curves and Cox regression analysis demonstrated the powerful predictive performance. ROC curves showed an improved survival prediction provided by this model. Functional analysis revealed positive association between risk score and CSC marker. These results had cross-dataset compatibility. Conclusions We established a novel four-gene signature based on CSC-related genes which could serve as a powerful prognostic tool in PDAC. Impact This signature can offer potential help for further improving current TNM staging system, and providing data for the development of novel personalized therapeutic strategies in the future.

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Ensemble of Gene Signatures Identifies Novel Biomarkers in Colorectal Cancer Activated through PPARγ and TNFα Signaling

Cited by 35 publications

References 37 publications

EGFR phosphorylation of DCBLD2 recruits TRAF6 and stimulates AKT-promoted tumorigenesis

EGFR phosphorylation of DCBLD2 recruits TRAF6 and stimulates AKT-promoted tumorigenesis

High expression of CD39/ENTPD1 in malignant epithelial cells of human rectal adenocarcinoma

Development and validation of a cancer stem cell-related signature for prognostic prediction in pancreatic ductal adenocarcinoma

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