title: Changes in PlGF and MET-HGF expressions in paired initial and recurrent glioblastoma.
abstract: Angiogenesis is one of the key features of glioblastoma (GB). However, the use of anti-angiogenic therapies directed against vascular endothelial growth factor (VEGF) is limited by primary or acquired resistance. MET/HGF and PlGF signaling are involved in potential alternative escape mechanisms to VEGF pathway. Our objective was to explore the potential changes of MET/HGF and PlGF expression, comparing initial diagnosis and recurrence after radiotherapy-temozolomide (RT/TMZ). Paired frozen tumors from both initial and recurrent surgery after radio-chemotherapy were available for 28 patients. RNA expressions of PlGF, MET, and HGF genes were analyzed by RT-qPCR. PlGF expression significantly decreased at recurrence (p = 0.021), and expression of MET showed a significant increase (p = 0.011) at recurrence. RNA expressions of MET and HGF significantly correlated both at baseline and recurrence (baseline: p = 0.005; recurrence: p = 0.019). Evolutive profile (increasing versus decreasing expression at recurrence) of MET was associated with PFS (p = 0.002) and OS (p = 0.022) at recurrence, while the evolutive profile of HGF was associated with PFS at relapse (p = 0.049). Recurrence of GB after chemo-radiation could be associated with a variation in PlGF and MET expression. These results contribute to suggest a modification of the GB angiogenic process between initial diagnosis and recurrence.
authors: Aix-Marseille Univ, 13284, Marseille, France. emeline.tabouret@gmail.com.|Department of Neuro-Oncology, APHM, Timone Hospital, 264, rue Saint Pierre, 13005, Marseille, France. emeline.tabouret@gmail.com.
authors: Emeline
authors: E
authors: Tabouret
authors: Aix-Marseille Univ, 13284, Marseille, France.
authors: Emilie
authors: E
authors: Denicolai
authors: Aix-Marseille Univ, 13284, Marseille, France.
authors: Christine
authors: C
authors: Delfino
authors: Aix-Marseille Univ, 13284, Marseille, France.|Department of Neuro-Surgery, APHM, Timone Hospital, 13005, Marseille, France.
authors: Thomas
authors: T
authors: Graillon
authors: Department of Neuro-Oncology, APHM, Timone Hospital, 264, rue Saint Pierre, 13005, Marseille, France.
authors: Celine
authors: C
authors: Boucard
authors: Transfer Laboratory, APHM, North Hospital, 13015, Marseille, France.
authors: Isabelle
authors: I
authors: Nanni
authors: Department of Radiotherapy, APHM, Timone Hospital, 13005, Marseille, France.
authors: Laetitia
authors: L
authors: Padovani
authors: Aix-Marseille Univ, 13284, Marseille, France.|Department of Anatomopathology, APHM, Timone Hospital, 13005, Marseille, France.
authors: Dominique
authors: D
authors: Figarella-Branger
authors: Aix-Marseille Univ, 13284, Marseille, France.|Department of Neuro-Oncology, APHM, Timone Hospital, 264, rue Saint Pierre, 13005, Marseille, France.
authors: Olivier
authors: O
authors: Chinot
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000532:radiotherapy; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000532:radiotherapy; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011878:Radiotherapy / Q000379:methods; D016019:Survival Analysis; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; C066855:HGF protein, human; D008565:Membrane Proteins; C098069:PIGF protein, human; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D003606:Dacarbazine; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D000077204:Temozolomide
keywords: Angiogenesis; Glioblastoma; HGF; MET; Paired; PlGF