In search for biomarkers and potential drug targets for uterine serous endometrial cancer

Gian Franco Zannoni, Francesco Fanfani, Giovanni Scambia, Giorgia Dinoi, Andrea Mariani, Enrica Martinelli, Alessandra Ciucci, Amy L Weaver, Gary L Keeney, George Vasmatzis, Panos Z Anastasiadis, Daniela Gallo

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Objective Serous endometrial cancer (USC) is a challenging malignancy associated with metastasis, recurrence and poor outcome. To identify clinically relevant prognostic biomarkers, we focused on a panel of proteins selected after a comprehensive literature review, for tumour profiling of a homogeneous cohort of USC patients. Methods Protein levels and localization were assessed by immunohistochemistry analysis in 36 hysterectomy samples. Tissue sections were stained with the following antibodies: Aurora A, phospho (T288) Aurora A, BRCA1, CHK1, CIP2A, Cyclin B1, Cyclin E, E2F-1, phospho (S364) E2F-1, FBXW7, FOXM1, phospho (S9) GSK3Beta, PLK1, phospho (T210) PLK1, PPP2R1B, p73, RAD51. Each marker was evaluated as a continuously-scaled variable for association with disease progression and death, using Cox proportional hazards models. The sample consisted of 36 patients with USC, half with stage III or IV disease. Results Results showed that higher CHK1 (Checkpoint kinase 1) expression was associated with a decreased risk of progression and death, after adjusting for stage. Interestingly, analysis of a TCGA data set of 109 USC patients corroborates our results showing a favourable prognostic role of CHEK1 after adjusting for stage. Higher FBXW7 (F-box and WD repeat domain containing 7) expression and higher cytoplasmic expression of PPP2R1B (Protein Phosphatase 2 A, Scaffold Subunit Abeta) were each associated with a decreased risk of progression, after adjusting for stage. Conclusions In conclusion, results from the present study identify new clinically relevant biomarkers and potential drug targets for uterine serous endometrial cancer.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaJournal of Cancer Research and Clinical Oncology
DOI
Stato di pubblicazionePubblicato - 2021

Keywords

  • Biomarkers
  • Drug targets
  • Uterine malignancy
  • Molecular profiling
  • Serous endometrial cancer
  • Immunochemistry

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