RESUMEN
BACKGROUND: The TP53 pathway is frequently inactivated in human cancers. PICT1 (also known as GLTSCR2) is a novel regulator of the MDM2-TP53 pathway via its interaction with the ribosomal protein RPL11 in the nucleolus. However, the clinical significance of PICT1 in gastric cancer remains unknown. METHODS: To evaluate PICT1 function, we used shRNA to inhibit PICT1 expression in gastric cancer cells that expressed wild-type TP53. PICT1 expression and TP53 mutation status were quantified in 110 cases of primary gastric cancer to explore the impact of PICT1 expression levels on gastric cancer. RESULTS: Deficiency of PICT1 significantly impaired cell proliferation and colony formation via TP53-mediated cell cycle arrest. Following induction of PICT1 deficiency, RPL11 translocated out of the nucleolus. Of the 110 gastric cancer samples tested, 70 (63.6%) and 40 (36.4%) tumours expressed wild-type and mutant TP53, respectively. In gastric cancer patients with wild-type TP53 tumours, patients with relatively low PICT1 expression levels had a better prognosis compared with high expression level patients (P=0.046). CONCLUSION: The findings suggest that PICT1 has a crucial role in gastric cancer progression by regulating the MDM2-TP53 pathway through RPL11. Clinically, PICT1 expression is a novel prognostic parameter in gastric cancer patients with wild-type TP53 tumours.
Asunto(s)
Proteínas Ribosómicas/metabolismo , Neoplasias Gástricas/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Nucléolo Celular/genética , Nucléolo Celular/metabolismo , Progresión de la Enfermedad , Humanos , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteínas Ribosómicas/genética , Transducción de Señal , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Proteína p53 Supresora de Tumor/biosíntesis , Proteína p53 Supresora de Tumor/genética , Proteínas Supresoras de Tumor/antagonistas & inhibidores , Proteínas Supresoras de Tumor/biosíntesis , Proteínas Supresoras de Tumor/genéticaRESUMEN
BACKGROUND: Parotid gland carcinoma is a rare and complicated histopathological classification. Therefore, assembling a sufficient number of cases with long-term outcomes in a single institute can present a challenge. METHOD: The medical records of 108 parotid gland carcinoma patients who were treated at Kyushu University Hospital, Fukuoka, Japan, between 1983 and 2014 were reviewed. The survival outcomes were analysed according to clinicopathological findings. RESULTS: Forty-six patients had low clinical stage tumours (I-II), and 62 patients had high clinical stage tumours (III-IV). Fifty-two, 10 and 46 patients had low-, intermediate- and high-grade tumours, respectively. Twenty-seven of 65 cases had positive surgical margins. In high clinical stage and intermediate- to high-grade tumours, adjuvant radiation therapy was correlated with local recurrence-free survival (p = 0.0244). Intermediate- to high-grade tumours and positive surgical margins were significantly associated with disease-specific survival in multivariate analysis (p = 0.0002 and p = 0.0058). CONCLUSION: The results of this study show that adjuvant radiation therapy is useful for improved local control in patients with high clinical stage and intermediate- to high-grade tumours.