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1.
Tumour Biol ; 39(7): 1010428317713492, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28720060

RESUMO

Although the oncogenic role of PPFIA1 (liprin-α1) in breast cancer has been reported, whether its dysregulation is associated with metastasis risk or survival outcomes in breast cancer patients is not clear. Our primary data showed that PPFIA1 expression was significantly higher in liver metastatic breast tumors than in the primary tumors. Then, we tried to pool previous annotated genomic data to assess the prognostic value of PPFIA1 in distant metastasis-free survival, the risk of metastatic relapse, and metastatic relapse-free survival in breast cancer patients by data mining in two large databases, Kaplan-Meier plotter and bc-GenExMiner 4.0. Results from Kaplan-Meier plotter showed that although high PPFIA1 expression was generally associated with decreased distant metastasis-free survival in estrogen receptor+ patients, subgroup analysis only confirmed significant association in estrogen receptor+/N- (nodal negative) group (median survival, high PPFIA1 group vs low PPFIA1 cohort: 191.21 vs 236.22 months; hazard ratio: 2.23, 95% confidence interval: 1.42-3.5, p < 0.001), but not in estrogen receptor+/N+ (nodal positive) group (hazard ratio: 1.63, 95% confidence interval: 0.88-3.03, p = 0.12). In estrogen receptor- patients, there was no association between PPFIA1 expression and distant metastasis-free survival, no matter in Nm (nodal status mixed), N-, or N+ subgroups. In bc-GenExMiner 4.0, Nottingham Prognostic Index- and Adjuvant! Online-adjusted analysis validated the independent prognostic value of PPFIA1 in metastatic risks in estrogen receptor+/N- patients. Based on these findings, we infer that high PPFIA1 expression might be an independent prognostic indicator of increased metastatic relapse risk in patients with estrogen receptor+/N- breast cancer, but not in estrogen receptor+/N+ or estrogen receptor- patients.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Biomarcadores Tumorais/biossíntese , Neoplasias da Mama/genética , Neoplasias Hepáticas/genética , Receptores de Estrogênio/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Recidiva
2.
Hum Pathol ; 78: 28-35, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29689245

RESUMO

Deletion of the frequently mutated AT-rich interacting domain-containing protein 1A (ARID1A), an SWI/SNF subunit, is associated with poor prognosis in various tumors. This study observed and analyzed ARID1A expression and its correlation with prognosis in gastric carcinoma. Postoperative sections of 98 patients with primary gastric cancer and 40 patients with gastric benign lesions were examined by immunohistochemistry. ARID1A deficiency was observed in 19.39% of gastric cancer tissues, 4.08% of matched paracancerous tissues, and 2.5% of normal gastric mucosa tissues. ARID1A expression was significantly down-regulated in gastric cancer tissues compared with paracancerous tissues (P = .001) and normal gastric mucosa tissues (P = .011). ARID1A deletion significantly correlated with tumor size (P = .022), lymph node metastasis (P = .030), and tumor differentiation (P = .009). In the 90 gastric cancer tissues with tumor stages II and III, the clinical outcome of the ARID1A-negative patients was significantly poorer than that of the ARID1A-positive patients (P = .005). Univariate analysis revealed that tumor invasion depth (P = .025), stage (P = .032), poor differentiation (P = .046), lymph node metastasis (P = .038), and ARID1A expression (P = .023) were significantly related to the overall survival of gastric cancer patients. Multivariate analysis demonstrated that tumor invasion depth (P = .029) and ARID1A expression (P = .031) were independent factors that indicate poor prognosis. In conclusion, the loss of ARID1A expression in gastric cancer patients significantly correlated with poor survival.


Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Proteínas Nucleares/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/terapia , Fatores de Transcrição/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Diferenciação Celular/fisiologia , Proteínas de Ligação a DNA , Regulação para Baixo , Feminino , Humanos , Imuno-Histoquímica/métodos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/diagnóstico
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