P53 overexpression and Ki67-index are associated with outcome in ductal pancreatic adenocarcinoma with adjuvant gemcitabine treatment

Striefler, Jana Kaethe; Sinn, Marianne; Pelzer, Uwe; Jühling, Anja; Wislocka, Lilianna; Bahra, Marcus; Sinn, Bruno Valentin; Denkert, Carsten; Dörken, Bernd; Oettle, Helmut; Riess, Hanno; Bläker, Hendrik; Lohneis, Philipp

doi:10.1016/j.prp.2016.06.001

Cited by 21 publications

(18 citation statements)

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“…As a well-known inhibitor of cell proliferation, p53 also promoted cell senescence to prevent the initiation of cancer [ 27 ]. Recent reports also showed that the positive expression of p53 was related to the late stage of pancreatic carcinoma [ 28 – 31 ].…”

Section: Discussionmentioning

confidence: 99%

GATA4 inhibits cell differentiation and proliferation in pancreatic cancer

Gong

Zhang

et al. 2018

PLoS ONE

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Pancreatic ductal carcinoma (PDAC) is a common malignant tumor of the digestive system. GATA4 is one of the transcriptional regulatory factors, which regulates the development of endoderm-derived organs, including heart and gut. GATA4 may act as a putative tumor suppressor gene. However, the role of GATA4 in pancreatic carcinogenesis is not yet clarified. This study showed that GATA4 was highly expressed in pancreatic cancer tissues, and its expression level was positively related to the grade of pathological differentiation, suggesting that it may contribute to the progression of pancreatic neoplasia. Ectopic expression of GATA4 gene reduced cell viability and interference of GATA4 expression significantly increased the colony formation ability of pancreatic cancer cells. Furthermore, GATA4 inhibited tumor growth in xenograft mice. Agilent expression microarray profiling analysis indicated that the genes with significant levels of differential expression in GATA4 over-expressing cells were enriched in the cell differentiation process. Analysis of KEGG signaling pathway demonstrated that the regulated genes were partially enriched in MAPK and JAK-STAT signaling pathways. Re-expression of GATA4 up-regulated P53 gene expression. Our data indicate that GATA4 gene might play a role in cell proliferation and differentiation during the progression of pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

GATA4 inhibits cell differentiation and proliferation in pancreatic cancer

Gong

Zhang

et al. 2018

PLoS ONE

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“…In fact, p53 protects cells against UV- and cisplatin-induced apoptosis in a manner dependent on transcription-coupled DNA repair [54], therefore its effect seems to be the result of an intricate network of signals and molecular interactions [55]. Moreover it has been recently reported in 162 tumors in pancreatic cancer patients that high proliferation of tumors and strong and consistent nuclear p53 expression by tumor cells (immunohistochemistry) is associated with a worse disease-free survival and overall survival in the overall study population [56]. In our study p53 mRNA resulted down-regulated in OVCAR3 and tended to be reduced in all cell lines.…”

Section: Discussionmentioning

confidence: 99%

In vitro effects of Apixaban on 5 different cancer cell lines

et al. 2017

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BackgroundCancer is associated with hypercoagulability. However, several data suggest that anticoagulant drugs may have an effect on tumor development and progression mediated by both coagulation dependent processes and non-coagulation dependent processes. Therefore, we investigated the in vitro effects of Apixaban on cell proliferation, mortality, cell migration, gene expression and matrix metalloproteinase in 5 different cancer cell lines.MethodsThe following cancer cell lines, and 2 normal fibroblast cultures (lung and dermal fibroblasts), were studied: OVCAR3 (ovarian cancer), MDA MB 231 (breast cancer), CaCO-2 (colon cancer), LNCaP (prostate cancer) and U937 (histiocytic lymphoma). Proliferation and cell mortality were assessed in control cells and Apixaban treated cultures (dose from 0.1 to 5 μg/ml, 0 to 96-h). Necrosis/Apoptosis (fluorescence microscopy), cell migration (24-h after scratch test), matrix metalloproteinase (MMP) activity and mRNA expression (RT PCR) of p16, p21, p53 and HAS were also assessed.ResultsHigh-dose (5 μg/ml) Apixaban incubation was associated with a significantly reduced proliferation in 3 cancer cell lines (OVCAR3, CaCO-2 and LNCaP) and with increased cancer cell mortality in all, except LNCaP, cancer lines. Apoptosis seems to account for the increased mortality. The migration capacity seems to be impaired after high-dose Apixaban incubation in OVCAR3 and CaCO-2 cells. Data on mRNA expression suggest a consistent increase in tumor suppression gene p16 in all cell lines.ConclusionsOur data suggest that high-dose Apixaban may be able to interfere with cancer cell in vitro, reducing proliferation and increasing cancer cell mortality through apoptosis in several cancer cell lines.

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“…CLUSTER1 also included up-regulated genes with unknown importance in pancreatic cancer, such as MATN3, SERPINA1, and IGFBP5. CLUSTER3 covered known prognostic biomarkers such as TOP2A (Tsiambas et al, 2007), CDK1 (Piao et al, 2019), and MKI67 (Striefler et al, 2016). This cluster was surrounded by genes (CENPK, ANLN, ECT2, and FAM83D) related to the cell cycle, but it appears that they were not included in the cluster due to the stringent confidence score cut-off criteria of the analysis.…”

Section: Protein-protein Interaction (Ppi) Networkmentioning

confidence: 99%

Integrated transcriptome meta-analysis of pancreatic ductal adenocarcinoma and matched adjacent pancreatic tissues

Atay

2020

PeerJ

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A comprehensive meta-analysis of publicly available gene expression microarray data obtained from human-derived pancreatic ductal adenocarcinoma (PDAC) tissues and their histologically matched adjacent tissue samples was performed to provide diagnostic and prognostic biomarkers, and molecular targets for PDAC. An integrative meta-analysis of four submissions (GSE62452, GSE15471, GSE62165, and GSE56560) containing 105 eligible tumor-adjacent tissue pairs revealed 344 differentially over-expressed and 168 repressed genes in PDAC compared to the adjacent-to-tumor samples. The validation analysis using TCGA combined GTEx data confirmed 98.24% of the identified up-regulated and 73.88% of the down-regulated protein-coding genes in PDAC. Pathway enrichment analysis showed that “ECM-receptor interaction”, “PI3K-Akt signaling pathway”, and “focal adhesion” are the most enriched KEGG pathways in PDAC. Protein-protein interaction analysis identified FN1, TIMP1, and MSLN as the most highly ranked hub genes among the DEGs. Transcription factor enrichment analysis revealed that TCF7, CTNNB1, SMAD3, and JUN are significantly activated in PDAC, while SMAD7 is inhibited. The prognostic significance of the identified and validated differentially expressed genes in PDAC was evaluated via survival analysis of TCGA Pan-Cancer pancreatic ductal adenocarcinoma data. The identified candidate prognostic biomarkers were then validated in four external validation datasets (GSE21501, GSE50827, GSE57495, and GSE71729) to further improve reliability. A total of 28 up-regulated genes were found to be significantly correlated with worse overall survival in patients with PDAC. Twenty-one of the identified prognostic genes (ITGB6, LAMC2, KRT7, SERPINB5, IGF2BP3, IL1RN, MPZL2, SFTA2, MET, LAMA3, ARNTL2, SLC2A1, LAMB3, COL17A1, EPSTI1, IL1RAP, AK4, ANXA2, S100A16, KRT19, and GPRC5A) were also found to be significantly correlated with the pathological stages of the disease. The results of this study provided promising prognostic biomarkers that have the potential to differentiate PDAC from both healthy and adjacent-to-tumor pancreatic tissues. Several novel dysregulated genes merit further study as potentially promising candidates for the development of more effective treatment strategies for PDAC.

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P53 overexpression and Ki67-index are associated with outcome in ductal pancreatic adenocarcinoma with adjuvant gemcitabine treatment

Cited by 21 publications

References 45 publications

GATA4 inhibits cell differentiation and proliferation in pancreatic cancer

GATA4 inhibits cell differentiation and proliferation in pancreatic cancer

In vitro effects of Apixaban on 5 different cancer cell lines

Integrated transcriptome meta-analysis of pancreatic ductal adenocarcinoma and matched adjacent pancreatic tissues

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