PROX1 is a predictor of survival for gliomas WHO grade II

Elsir, Tamador; Qu, Mingqi; Berntsson, Shala Ghaderi; Orrego, Abiel; Olofsson, Tommie; Lindström, Mikael S.; Nistér, Monica; Deimling, Andreas von; Hartmann, Christian; Ribom, Dan; Smits, Anja

doi:10.1038/bjc.2011.162

Cited by 34 publications

(47 citation statements)

References 31 publications

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“…Together with our previous study in low-grade gliomas [12], we propose that PROX1 is a clinically valuable biomarker to predict the course of disease for these patients. Future studies are needed to clarify the mechanisms by which PROX1 leads to tumor progression and affects clinical outcome in this patient group.…”

Section: Discussionsupporting

confidence: 60%

PROX1 is a novel pathway-specific prognostic biomarker for high-grade astrocytomas; results from independent glioblastoma cohorts stratified by age and IDH mutation status

et al. 2016

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PROX1 is a transcription factor with an essential role in embryonic development and determination of cell fate. In addition, PROX1 has been ascribed suppressive as well as oncogenic roles in several human cancers, including brain tumors. In this study we explored the correlation between PROX1 expression and patient survival in high-grade astrocytomas. For this purpose, we analyzed protein expression in tissue microarrays of tumor samples stratified by patient age and IDH mutation status. We initially screened 86 unselected high-grade astrocytomas, followed by 174 IDH1-R132H1 immunonegative glioblastomas derived from patients aged 60 years and older enrolled in the Nordic phase III trial of elderly patients with newly diagnosed glioblastoma. Representing the younger population of glioblastomas, we studied 80 IDH-wildtype glioblastomas from patients aged 18-60 years. There was no correlation between PROX1 protein and survival for patients with primary glioblastomas included in these cohorts. In contrast, high expression of PROX1 protein predicted shorter survival in the group of patients with IDH-mutant anaplastic astrocytomas and secondary glioblastomas. The prognostic impact of PROX1 in IDH-mutant 1p19q non-codeleted high-grade astrocytomas, as well as the negative findings in primary glioblastomas, was corroborated by gene expression data extracted from the Cancer Genome Atlas. We conclude that PROX1 is a new prognostic biomarker for 1p19q non-codeleted high-grade astrocytomas that have progressed from pre-existing low-grade tumors and harbor IDH mutations.

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Section: Discussionsupporting

confidence: 60%

PROX1 is a novel pathway-specific prognostic biomarker for high-grade astrocytomas; results from independent glioblastoma cohorts stratified by age and IDH mutation status

et al. 2016

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“…Decreased expression of PROX1 is observed in pancreatic cancers, hepatocellular carcinomas, sporadic breast cancers, and biliary carcinomas, indicating that PROX1 plays a tumor-suppressive role in these cancers [9][10][11][12]. In contrast, overexpression of PROX1 is observed in colorectal cancers, endothelial tumors, and gliomas, indicating that PROX1 promotes the progression of these cancers [13][14][15][16]. These data suggest that PROX1 could be a potential molecular target for treating human cancers.…”

Section: Introductionmentioning

confidence: 65%

Prospero homeobox 1 mediates the progression of gastric cancer by inducing tumor cell proliferation and lymphangiogenesis

et al. 2016

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Background Prospero homeobox 1 (PROX1) functions as a tumor suppressor gene or an oncogene in various cancer types. However, the distinct function of PROX1 in gastric cancer is unclear. We determined whether PROX1 affected the oncogenic behavior of gastric cancer cells and investigated its prognostic value in patients with gastric cancer. Methods A small interfering RNA against PROX1 was used to silence PROX1 expression in gastric cancer cell lines AGS and SNU638. Expression of PROX1 in gastric cancer tissues was investigated by performing immunohistochemistry. Apoptosis, proliferation, angiogenesis, and lymphangiogenesis were determined by performing the TUNEL assay and immunohistochemical staining for Ki-67, CD34, and D2-40. Results PROX1 knockdown induced apoptosis by activating cleaved caspase-3, caspase-7, caspase-9, and poly(ADP-ribose) polymerase, and by decreasing the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. PROX1 knockdown also suppressed tumor cell proliferation. In addition, PROX1 knockdown decreased lymphatic endothelial cell invasion and tube formation and the expression of vascular endothelial growth factor (VEGF)-C and -D and cyclooxygenase (COX)-2. However, PROX1 knockdown only decreased umbilical vein endothelial cell invasion, not tube formation. The mean Ki-67 labeling index and lymphatic vessel density value of PROX1-positive tumors were significantly higher than those of PROX1-negative tumors. However, no significant difference was observed between PROX1 expression and apoptotic index or microvessel density. PROX1 expression was significantly associated with age, cell differentiation, lymph node metastasis, cancer stage, and poor survival. Conclusions These results indicate that PROX1 mediates the progression of gastric cancer by inducing tumor cell proliferation and lymphangiogenesis.

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“…In Kaposiform hemangioendothelioma, overexpression of PROX1 is associated with more aggressive tumor behaviour by inducing genes involved in cell migration and adhesion, thus enabling infiltration into surrounding tissues [18,19]. Gliomas of the central nervous system also express PROX1 [18]. Now, rectal NETs can be added to this list of PROX1-positive tumors, since we detected PROX1 positivity of in about one half of the rectal NETs.…”

Section: Discussionmentioning

confidence: 87%

“…In colorectal adenocarcinomas, PROX1 predicts aggressive clinical course and poor survival [7]. In Kaposiform hemangioendothelioma, overexpression of PROX1 is associated with more aggressive tumor behaviour by inducing genes involved in cell migration and adhesion, thus enabling infiltration into surrounding tissues [18,19]. Gliomas of the central nervous system also express PROX1 [18].…”

Section: Discussionmentioning

confidence: 98%

PROX1 is involved in progression of rectal neuroendocrine tumors, NETs

et al. 2015

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PROX1 is a homeobox transcription factor involved in the development of the lens, liver and heart and found upregulated in colorectal cancers. We studied PROX1 expression by immunohistochemistry in rectal neuroendocrine tumors (NETs). Approximately 10 to 15 % of gastroenteropancreatic NETs occur in the rectum, and some may metastasize. Yet little is known about the molecular pathogenesis of rectal NETs or their metastasis propensity. The objectives were to find out whether PROX1 plays a role in progression of rectal NETs and whether it has value as prognostic marker. In grading of rectal NETs, we applied the WHO 2010 classification. We carried out immunohistochemical staining of PROX1 on 72 primary tumors and six metastases and evaluated nuclear positivity in each tumor. Correlation between PROX1 expression, metastasis and patient survival was then assessed. Annexin A1, a downstream target of PROX1, was immunohistochemically assessed in 18 tumors. PROX1 protein was detected in about half of the tumors, with stronger expression in metastasized cases. PROX1 expression correlated with tumor metastasis and patient prognosis. Annexin A1 was negative in most of the high-grade tumors correlating strongly with grade and metastatic potential. Our results indicate that immunohistochemical detection of PROX1 correlates with a more malignant phenotype in rectal NETs. High PROX1 expression was associated with increased metastatic potential and poor patient survival but not as strongly as grade by the WHO 2010 classification. PROX1 may be involved in progression of rectal NETs as a part of the Wnt pathway.

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PROX1 is a predictor of survival for gliomas WHO grade II

Cited by 34 publications

References 31 publications

PROX1 is a novel pathway-specific prognostic biomarker for high-grade astrocytomas; results from independent glioblastoma cohorts stratified by age and IDH mutation status

PROX1 is a novel pathway-specific prognostic biomarker for high-grade astrocytomas; results from independent glioblastoma cohorts stratified by age and IDH mutation status

Prospero homeobox 1 mediates the progression of gastric cancer by inducing tumor cell proliferation and lymphangiogenesis

PROX1 is involved in progression of rectal neuroendocrine tumors, NETs

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