Hyper-phosphorylation of Rb S249 together with CDK5R2/p39 overexpression are associated with impaired cell adhesion and epithelial-to-mesenchymal transition: Implications as a potential lung cancer grading and staging biomarker.

Autor: Pérez-Morales J; Biochemistry and Cancer Biology Divisions, Basic Science Department, Ponce Health Sciences University-Ponce Research Institute, Ponce, Puerto Rico., Mejías-Morales D; Biochemistry and Cancer Biology Divisions, Basic Science Department, Ponce Health Sciences University-Ponce Research Institute, Ponce, Puerto Rico., Rivera-Rivera S; Biochemistry and Cancer Biology Divisions, Basic Science Department, Ponce Health Sciences University-Ponce Research Institute, Ponce, Puerto Rico., González-Flores J; Biochemistry and Cancer Biology Divisions, Basic Science Department, Ponce Health Sciences University-Ponce Research Institute, Ponce, Puerto Rico., González-Loperena M; Biochemistry and Cancer Biology Divisions, Basic Science Department, Ponce Health Sciences University-Ponce Research Institute, Ponce, Puerto Rico., Cordero-Báez FY; Biochemistry and Cancer Biology Divisions, Basic Science Department, Ponce Health Sciences University-Ponce Research Institute, Ponce, Puerto Rico., Pedreira-García WM; Biochemistry and Cancer Biology Divisions, Basic Science Department, Ponce Health Sciences University-Ponce Research Institute, Ponce, Puerto Rico., Chardón-Colón C; Biochemistry and Cancer Biology Divisions, Basic Science Department, Ponce Health Sciences University-Ponce Research Institute, Ponce, Puerto Rico., Cabán-Rivera J; Biochemistry and Cancer Biology Divisions, Basic Science Department, Ponce Health Sciences University-Ponce Research Institute, Ponce, Puerto Rico., Cress WD; Molecular Oncology and Thoracic Oncology Departments, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America., Gordian ER; Molecular Oncology and Thoracic Oncology Departments, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America., Muñoz-Antonia T; Molecular Oncology and Thoracic Oncology Departments, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America., Cabrera-Ríos M; Department of Industrial Engineering, University of Puerto Rico at Mayagüez, Mayagüez, Puerto Rico., Isidro A; Physiology Division, Basic Science Department, Ponce Health Sciences University-Ponce Research Institute, Ponce, Puerto Rico., Coppola D; Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America., Rosa M; Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America., Boyle TA; Anatomic Pathology, Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America., Izumi V; Proteomics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America., Koomen JM; Molecular Oncology and Thoracic Oncology Departments, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, United States of America., Santiago-Cardona PG; Biochemistry and Cancer Biology Divisions, Basic Science Department, Ponce Health Sciences University-Ponce Research Institute, Ponce, Puerto Rico.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2018 Nov 19; Vol. 13 (11), pp. e0207483. Date of Electronic Publication: 2018 Nov 19 (Print Publication: 2018).
DOI: 10.1371/journal.pone.0207483
Abstrakt: Prediction of lung cancer metastasis relies on post-resection assessment of tumor histology, which is a severe limitation since only a minority of lung cancer patients are diagnosed with resectable disease. Therefore, characterization of metastasis-predicting biomarkers in pre-resection small biopsy specimens is urgently needed. Here we report a biomarker consisting of the phosphorylation of the retinoblastoma protein (Rb) on serine 249 combined with elevated p39 expression. This biomarker correlates with epithelial-to-mesenchymal transition traits in non-small cell lung carcinoma (NSCLC) cells. Immunohistochemistry staining of NSCLC tumor microarrays showed that strong phospho-Rb S249 staining positively correlated with tumor grade specifically in the squamous cell carcinoma (SCC) subtype. Strong immunoreactivity for p39 positively correlated with tumor stage, lymph node invasion, and distant metastases, also in SCC. Linear regression analyses showed that the combined scoring for phospho-Rb S249, p39 and E-cadherin in SCC is even more accurate at predicting tumor staging, relative to each score individually. We propose that combined immunohistochemistry staining of NSCLC samples for Rb phosphorylation on S249, p39, and E-cadherin protein expression could aid in the assessment of tumor staging and metastatic potential when tested in small primary tumor biopsies. The intense staining for phospho-Rb S249 that we observed in high grade SCC could also aid in the precise sub-classification of poorly differentiated SCCs.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje