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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalJournal of Cancer Research and Clinical Oncology
DOIs
StateAccepted/In press - 2021

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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