human
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: INTRODUCTION The homeobox-containing transcription factor muscle segment homeobox 2 ( Msx2 ) plays an important role in mammary gland development . However , the clinical implications of Msx2 expression in breast cancer are unclear . The aims of this study were to investigate the potential clinical value of Msx2 as a breast cancer biomarker and to clarify its functional role in vitro . METHODS Msx2 gene expression was first examined in a well-validated breast cancer transcriptomic dataset of 295 patients . Msx2 protein expression was then evaluated by immunohistochemistry in a tissue microarray ( TMA ) containing 281 invasive breast tumours . Finally , to assess the functional role of Msx2 in vitro , Msx2 was ectopically expressed in a highly invasive breast tumour cell line ( MDA-MB-231 ) and an immortalised breast cell line ( MCF10a ) , and these cell lines were examined for changes in growth rate , cell death and cell signalling . RESULTS Examination of Msx2 mRNA expression in a breast cancer transcriptomic dataset demonstrated that increased levels of Msx2 were associated with good prognosis ( P = 0.011 ) . Evaluation of Msx2 protein expression on a TMA revealed that Msx2 was detectable in both tumour cell nuclei and cytoplasm . Cytoplasmic Msx2 expression was associated with low grade tumours ( P = 0.012 ) and Ki67 negativity ( P = 0.018 ) . Nuclear Msx2 correlated with low-grade tumours ( P = 0.015 ) , estrogen receptor positivity ( P = 0.038 ) , low Ki67 ( P = 0.005 ) and high cyclin D1 expression ( P = 0.037 ) . Increased cytoplasmic Msx2 expression was associated with a prolonged breast cancer-specific survival ( P = 0.049 ) , recurrence-free survival ( P = 0.029 ) and overall survival ( P = 0.019 ) . Ectopic expression of Msx2 in breast cell lines resulted in radically decreased cell viability mediated by induction of cell death via apoptosis . Further analysis of Msx2-expressing cells revealed increased levels of p21 and phosphorylated extracellular signal-regulated kinase ( ERK ) and decreased levels of Survivin and the ' split ends ' ( SPEN ) protein family member RBM15 . CONCLUSIONS We conclude that increased Msx2 expression results in improved outcome for breast cancer patients , possibly by increasing the likelihood of tumour cell death by apoptosis .
    OUTPUT:

agent
sustaining proliferative signaling;resisting cell death;evading growth suppressors
The task is to decide the Hallmarks of Cancer (HOC) taxonomy of the article based on its abstract. The input is an abstract text. There are 10 topics you will need to decide whether the article is related to. Topics: sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, activating invasion and metastasis, genomic instability and mutation, tumor promoting inflammation, cellular energetics, avoiding immune destruction. The output should be topics from the above 10 topics, that are related to the input article. Please note one article can be related to multiple topics. Output format: provide a semicolon-separated list of relevant topics.
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    INPUT: INTRODUCTION The homeobox-containing transcription factor muscle segment homeobox 2 ( Msx2 ) plays an important role in mammary gland development . However , the clinical implications of Msx2 expression in breast cancer are unclear . The aims of this study were to investigate the potential clinical value of Msx2 as a breast cancer biomarker and to clarify its functional role in vitro . METHODS Msx2 gene expression was first examined in a well-validated breast cancer transcriptomic dataset of 295 patients . Msx2 protein expression was then evaluated by immunohistochemistry in a tissue microarray ( TMA ) containing 281 invasive breast tumours . Finally , to assess the functional role of Msx2 in vitro , Msx2 was ectopically expressed in a highly invasive breast tumour cell line ( MDA-MB-231 ) and an immortalised breast cell line ( MCF10a ) , and these cell lines were examined for changes in growth rate , cell death and cell signalling . RESULTS Examination of Msx2 mRNA expression in a breast cancer transcriptomic dataset demonstrated that increased levels of Msx2 were associated with good prognosis ( P = 0.011 ) . Evaluation of Msx2 protein expression on a TMA revealed that Msx2 was detectable in both tumour cell nuclei and cytoplasm . Cytoplasmic Msx2 expression was associated with low grade tumours ( P = 0.012 ) and Ki67 negativity ( P = 0.018 ) . Nuclear Msx2 correlated with low-grade tumours ( P = 0.015 ) , estrogen receptor positivity ( P = 0.038 ) , low Ki67 ( P = 0.005 ) and high cyclin D1 expression ( P = 0.037 ) . Increased cytoplasmic Msx2 expression was associated with a prolonged breast cancer-specific survival ( P = 0.049 ) , recurrence-free survival ( P = 0.029 ) and overall survival ( P = 0.019 ) . Ectopic expression of Msx2 in breast cell lines resulted in radically decreased cell viability mediated by induction of cell death via apoptosis . Further analysis of Msx2-expressing cells revealed increased levels of p21 and phosphorylated extracellular signal-regulated kinase ( ERK ) and decreased levels of Survivin and the ' split ends ' ( SPEN ) protein family member RBM15 . CONCLUSIONS We conclude that increased Msx2 expression results in improved outcome for breast cancer patients , possibly by increasing the likelihood of tumour cell death by apoptosis .
    OUTPUT:
