scholarly journals Prognostic Significance of Stem Cell/ Epithelial-Mesenchymal Transition Markers in Periampullary/Pancreatic Cancers: FGFR1 Is A Promising Marker.

2020 ◽  
Author(s):  
Yosep Chong ◽  
Nishant Thakur ◽  
Kwang Yeol Paik ◽  
Eun Jung Lee ◽  
Chang Suk Kang
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Tumor Recurrence ◽  
Epithelial Mesenchymal Transition ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Stem Cell Markers ◽  
Mesenchymal Transition ◽  
Clinicopathologic Parameters ◽  
Emt Markers

Abstract Background: Periampullary cancers (PAC) including pancreatic, ampulla of Vater (AOV), and common bile duct (CBD) cancers are highly aggressive with a lack of useful prognostic markers beyond T stage. However, T staging can be biased due to the anatomic complexity of this region. Recently, several markers related to cancer stem cells and epithelial-mesenchymal transition (EMT) such as octamer transcription factor-4 (Oct4) and fibroblast growth factor receptor 1 (FGFR1) respectively, have been proposed as new promising markers in other solid cancers. The aim of this study was to assess the expression and prognostic significance of stem cell/EMT markers in PACs. Methods : Formalin-fixed, paraffin-embedded tissues of surgically excised PACs from the laboratory archives from 1998 to 2014 were evaluated by immunohistochemical staining for stem cell/EMT markers using tissue microarray. The clinicopathologic parameters were documented and statistically analyzed with the immunohistochemical findings. Survival and recurrence data were collected and analyzed. Results: A total of 126 PAC cases were evaluated. The average age was 63 years, with 76 male and 50 female patient samples. Age less than 74 years, AOV cancers, lower T & N stage, lower tumor size, no lymphatic, vascular, perineural invasion and histologic well differentiation, intestinal type, no fibrosis, severe inflammation were significantly associated with the better overall survival High expression levels of FGFR1 as well as CK20, CDX2, and VEGF were significantly related to better overall survival, while other stem cell markers were not related. Similar findings were observed for tumor recurrence using disease-free survival. Conclusions: In addition to other clinicopathologic parameters, severe fibrosis was related to frequent tumor recurrence, and high FGFR1 expression was associated with better overall survival. Histologic changes such as extensive fibrosis need to be investigated further in relation to EMT of PACs.

scholarly journals Prognostic Significance of Stem Cell/ Epithelial-Mesenchymal Transition Markers in Periampullary/Pancreatic Cancers: FGFR1 Is A Promising Marker.

2019 ◽  
Author(s):  
Yosep Chong ◽  
Nishant Thakur ◽  
Kwang Yeol Paik ◽  
Eun Jung Lee ◽  
Chang Suk Kang
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Tumor Recurrence ◽  
Epithelial Mesenchymal Transition ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Stem Cell Markers ◽  
Mesenchymal Transition ◽  
Clinicopathologic Parameters ◽  
Emt Markers

Abstract Background: Periampullary cancers (PAC) including pancreatic, ampulla of Vater (AOV), and common bile duct (CBD) cancers are highly aggressive with a lack of useful prognostic markers beyond T stage. However, T staging can be biased due to the anatomic complexity of this region. Recently, several markers related to cancer stem cells and epithelial-mesenchymal transition (EMT) such as octamer transcription factor-4 (Oct4) and fibroblast growth factor receptor 1 (FGFR1) respectively, have been proposed as new promising markers in other solid cancers. The aim of this study was to assess the expression and prognostic significance of stem cell/EMT markers in PACs. Methods : Formalin-fixed, paraffin-embedded tissues of surgically excised PACs from the laboratory archives from 1998 to 2014 were evaluated by immunohistochemical staining for stem cell/EMT markers using tissue microarray. The clinicopathologic parameters were documented and statistically analyzed with the immunohistochemical findings. Survival and recurrence data were collected and analyzed. Results: A total of 126 PAC cases were evaluated. The average age was 63 years, with 76 male and 50 female patient samples. Age less than 74 years, AOV cancers, lower T & N stage, lower tumor size, no lymphatic, vascular, perineural invasion and histologic well differentiation, intestinal type, no fibrosis, severe inflammation were significantly associated with the better overall survival High expression levels of FGFR1 as well as CK20, CDX2, and VEGF were significantly related to better overall survival, while other stem cell markers were not related. Similar findings were observed for tumor recurrence using disease-free survival. Conclusions: In addition to other clinicopathologic parameters, severe fibrosis was related to frequent tumor recurrence, and high FGFR1 expression was associated with better overall survival. Histologic changes such as extensive fibrosis need to be investigated further in relation to EMT of PACs.

scholarly journals Prognostic Significance of Stem Cell/ Epithelial-Mesenchymal Transition Markers in Periampullary/Pancreatic Cancers: FGFR1 Is A Novel Marker.

2019 ◽  
Author(s):  
Yosep Chong ◽  
Nishant Thakur ◽  
Kwang Yeol Paik ◽  
Eun Jung Lee ◽  
Chang Suk Kang
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Tumor Recurrence ◽  
Epithelial Mesenchymal Transition ◽  
Prognostic Significance ◽  
Stem Cell Markers ◽  
Mesenchymal Transition ◽  
T Stage ◽  
Clinicopathologic Parameters ◽  
Emt Markers

Abstract Background: Periampullary cancers (PAC) including pancreatic, ampulla of Vater (AOV), and common bile duct (CBD) cancers are highly aggressive with lack of useful prognostic markers beyond T stage. However, T staging can be biased due to the anatomic complexity of this region. Recently, several markers related to cancer stem cells and epithelial-mesenchymal transition (EMT) such as octamer transcription factor-4 (Oct4) and fibroblast growth factor receptor 1 (FGFR1) respectively, have been proposed as new promising markers in other solid cancers. The aim of this study was to access the expression and prognostic significance of stem cell/EMT markers in PACs.Methods: Formalin-fixed, paraffin-embedded tissues of surgically excised PACs from the laboratory archives from 1998 to 2014 were evaluated by immunohistochemical staining for stem cell/EMT markers using tissue microarray. The clinicopathologic parameters were documented and statistically analyzed with the immunohistochemical findings. Survival and recurrence data were collected and analyzed.Results: A total of 126 PAC cases were evaluated. The average age was 63 years, with 76 male and 50 female patient samples. The overall survival was statistically related to old age (over 74 years), tumor epicenter (pancreas < CBD < AOV), T stage, tumor size, N stage, lymphatic, vascular, perineural invasion, histologic grade (differentiation), subtype (pancreaticobiliary type < intestinal type), degree of fibrosis, and inflammation. The expression levels of FGFR1 as well as CK20, CDX2, and VEGF were significantly related to overall survival while other stem cell markers were not related. Similar findings were observed for tumor recurrence using disease-free survival. Conclusions: In addition to other clinicopathologic parameters, the degree of fibrosis and expression of FGFR1 were novel markers for overall survival and tumor recurrence. Histologic changes such as extensive fibrosis needs to be investigated further in relation to EMT of PACs.

High microRNA-28-5p expression in colorectal adenocarcinoma predicts short-term relapse of node-negative patients and poor overall survival of patients with non-metastatic disease

2018 ◽  
Vol 56 (6) ◽  
pp. 990-1000 ◽  
Author(s):  
Panagiotis Tsiakanikas ◽  
Christos K. Kontos ◽  
Dimitrios Kerimis ◽  
Iordanis N. Papadopoulos ◽  
Andreas Scorilas
Keyword(s):  
Overall Survival ◽  
Reverse Transcription ◽  
Colorectal Adenocarcinoma ◽  
Quantitative Polymerase Chain Reaction ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Colorectal Tumors ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis ◽  
Total Rna

Abstract Background: MicroRNAs (miRNAs) may function either as oncogenes or tumor suppressors and are heavily involved in the initiation and progression of cancer, and in metastasis of tumor cells. MicroRNA-28-5p (miR-28-5p) targets several cancer-related genes and is hence involved in cell proliferation, migration, invasion and epithelial-mesenchymal transition. In this study, we investigated the potential diagnostic and prognostic significance of miR-28-5p expression in colorectal adenocarcinoma, the most frequent type of colorectal cancer (CRC). Methods: Therefore, we isolated total RNA from 182 colorectal adenocarcinoma specimens and 86 paired non-cancerous colorectal mucosae. After polyadenylation of 2 μg total RNA and its reverse transcription using an oligo-dT-adapter primer, we quantified miR-28-5p levels using an in-house-developed reverse-transcription real-time quantitative polymerase chain reaction (RT-qPCR) method, based on the SYBR Green chemistry. Results: Comparison of miR-28-5p levels among 86 pairs of colorectal tumors and their adjacent non-cancerous mucosae uncovered the downregulation of miR-28-5p expression in the majority of malignant colorectal tumors. More importantly, high miR-28-5p expression predicts poor disease-free survival (DFS) and overall survival (OS) of colorectal adenocarcinoma patients. Multivariate Cox regression analysis revealed that miR-28-5p overexpression is a significant predictor of poor prognosis in colorectal adenocarcinoma, independent of tumor size, histological grade, TNM staging, radiotherapy and chemotherapy. Interestingly, strong miR-28-5p expression retains its predictive potential regarding relapse among patients with negative regional lymph nodes, and predicts poor OS in patients diagnosed with non-metastatic colorectal adenocarcinoma. Conclusions: High miR-28-5p expression predicts poor DFS and OS of colorectal adenocarcinoma patients, independently of clinicopathological prognosticators and standard patient treatment, including radiotherapy and chemotherapy.

scholarly journals Resveratrol Suppresses Epithelial-Mesenchymal Transition in GBM by Regulating Smad-Dependent Signaling

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Yang Song ◽  
Yong Chen ◽  
Yunqian Li ◽  
Xiaoyan Lyu ◽  
Jiayue Cui ◽  
...  
Keyword(s):  
Stem Cell ◽  
Epithelial Mesenchymal Transition ◽  
Inhibitory Effect ◽  
Stem Cell Markers ◽  
Invasive Ability ◽  
Self Renewal ◽  
Invasive Phenotype ◽  
Mesenchymal Transition ◽  
Cancer Stem Cell Markers

Glioblastoma (GBM) is the most common and malignant intracranial tumor in adults. Despite continuous improvements in diagnosis and therapeutic method, the prognosis is still far away from expectations. The invasive phenotype of GBM is the main reason for the poor prognosis. Epithelial-mesenchymal transition (EMT) is recognized as a participator in this invasive phenotype. Resveratrol, a natural plant-derived compound, is reported to be able to regulate EMT. In the present study, we used TGF-β1 to induce EMT and aimed to evaluate the effect of resveratrol on EMT and to explore the underline mechanism in GBM. Western blotting was used to detect the expression of EMT-related markers, stemness markers, and Smad-dependent signaling. Wound healing assay and transwell invasion assay were performed to evaluate the migratory and invasive ability of GBM cells. Gliosphere formation assay was used to investigate the effect of resveratrol on the ability of self-renewal. Xenograft experiment was conducted to examine the effect of resveratrol on EMT and Smad-dependent signalingin vivo. Our data validated that resveratrol suppressed EMT and EMT-associated migratory and invasive ability via Smad-dependent signaling in GBM cells. We also confirmed that resveratrol obviously inhibited EMT-induced self-renewal ability of glioma stem cells (GSCs) and inhibited EMT-induced cancer stem cell markers Bmi1 and Sox2, suggesting that resveratrol is able to suppress EMT-generated stem cell-like properties in GBM cells. Furthermore, we also showed the inhibitory effect of resveratrol on EMT in xenograft experimentsin vivo. Overall, our study reveals that resveratrol suppresses EMT and EMT-generated stem cell-like properties in GBM by regulating Smad-dependent signaling and provides experimental evidence of resveratrol for GBM treatment.

MET overexpression as a hallmark of the epithelial-mesenchymal transition (EMT) phenotype in colorectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3529-3529 ◽  
Author(s):  
Kanwal Pratap Singh Raghav ◽  
Hesham M. Amin ◽  
Wenting Wang ◽  
Ganiraju C. Manyam ◽  
Bradley Broom ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Overall Survival ◽  
Protein Expression ◽  
Protein Gene ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Gene Signatures ◽  
Protein Levels ◽  
Emt Markers

3529 Background: Epithelial-mesenchymal transition (EMT) has been identified as a dominant molecular subtype of colorectal cancer (CRC). This EMT phenotype as recognized by complex gene signatures is prognostic and associated with chemoresistance, but a biomarker for EMT suitable for clinical utilization has not yet been validated. The purpose of this study was to compare MET protein expression with protein/gene expression of EMT markers and to evaluate its impact on overall survival (OS). Methods: We performed an exploratory analysis of 139 untreated primary CRC samples using data from The Cancer Genome Atlas. Protein and gene expressions were measured using reverse-phase protein array (RPPA) and RNA-sequencing, respectively. MET high/overexpressed group was defined by protein level in the highest quartile. Mann-Whitney U-test and Spearman rank correlation was used to determine association between MET protein expression and protein/gene expression of EMT markers and EMT gene signature scores. Regression tree method and Kaplan-Meier estimates were used to assess overall survival (OS). Results: The MET protein distribution is right skewed, demonstrating a unique population of MET high expressing tumors (P < 0.01). Colon tumors had higher MET protein levels compared to rectal tumors (P < 0.01). MET overexpression was associated with decreased OS (HR 2.92; 95% CI: 1.45 - 5.92). MET protein expression correlated strongly with protein expressions of SLUG (transcription factor for EMT) (r = 0.6) and ERCC1 (a marker for oxaliplatin chemo-resistance) (r = 0.6) (P < 0.01). Higher MET protein levels were associated with higher gene expression of 28 EMT markers including AXL, VIM, ZEB1, ZEB2, FGF1, TGFB1I1 and MMP11 (P < 0.05). Higher MET protein levels were also associated with higher gene scores derived from three published EMT gene signatures (P < 0.05). MET protein expression did not correlate with MET gene expression (r = 0.16). Conclusions: Increased MET protein expression strongly correlates with a molecular EMT phenotype and poor survival in patients with CRC. MET protein expression may be used as a surrogate biomarker to represent and select for this unique molecular subset of CRC driven by EMT biology.

scholarly journals Effect of NR5A2 inhibition on pancreatic cancer stem cell (CSC) properties and epithelial-mesenchymal transition (EMT) markers

2017 ◽  
Vol 56 (5) ◽  
pp. 1438-1448 ◽  
Author(s):  
Zhaofan Luo ◽  
Yanan Li ◽  
Mingxin Zuo ◽  
Chang Liu ◽  
Dong Yan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Emt Markers

scholarly journals Expression of Stem Cell and Epithelial-Mesenchymal Transition Markers in Circulating Tumor Cells of Breast Cancer Patients

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Natalia Krawczyk ◽  
Franziska Meier-Stiegen ◽  
Malgorzata Banys ◽  
Hans Neubauer ◽  
Eugen Ruckhaeberle ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Breast ◽  
Current Data ◽  
Stem Cell Markers ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition

Evaluation and characterization of circulating tumor cells (CTCs) have become a major focus of translational cancer research. Presence of CTCs predicts worse clinical outcome in early and metastatic breast cancer. Whether all cells from the primary tumor have potential to disseminate and form subsequent metastasis remains unclear. As part of the metastatic cascade, tumor cells lose their cell-to-cell adhesion and undergo epithelial-mesenchymal transition (EMT) in order to enter blood circulation. During EMT epithelial antigens are downregulated; thus, such tumor cells might elude classical epithelial marker-based detection. Several researchers postulated that some CTCs express stem cell-like phenotype; this might lead to chemoresistance and enhanced metastatic potential of such cells. In the present review, we discuss current data on EMT and stem cell markers in CTCs of breast cancer and their clinical significance.

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