Pre-treatment Serum HE4 Level as a Novel Independent Prognostic Biomarker for Uterine Cervical Carcinoma Patients

Eliana Bignotti; Laura Zanotti; Paola Todeschini; Valentina Zizioli; Chiara Romani; Davide Capoferri; Germana Tognon; Enrico Sartori; Stefano Calza; Franco Odicino; Antonella Ravaggi

doi:10.3389/fonc.2020.584022

Pre-treatment Serum HE4 Level as a Novel Independent Prognostic Biomarker for Uterine Cervical Carcinoma Patients

Front Oncol. 2020 Sep 29:10:584022. doi: 10.3389/fonc.2020.584022. eCollection 2020.

Authors

Eliana Bignotti^{1

2}, Laura Zanotti^{1

2}, Paola Todeschini², Valentina Zizioli¹, Chiara Romani², Davide Capoferri², Germana Tognon¹, Enrico Sartori^{1

3}, Stefano Calza^{4

5

6}, Franco Odicino^{1

2

3}, Antonella Ravaggi^{1

2

3}

Affiliations

¹ Division of Obstetrics and Gynecology, Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili di Brescia, Brescia, Italy.
² "Angelo Nocivelli" Institute of Molecular Medicine, University of Brescia and ASST-Spedali Civili of Brescia, Brescia, Italy.
³ Department of Clinical and Experimental Sciences, Division of Obstetrics and Gynecology University of Brescia, Brescia, Italy.
⁴ Unit of Medical Statistics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
⁵ Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
⁶ Big & Open Data Innovation Laboratory (BODAI) Lab, University of Brescia, Brescia, Italy.

Abstract

In spite of the effective implementation of screening programs, uterine cervical carcinoma (UCC) remains one of the major causes of cancer death among women around the world. The aim of this study was to investigate the prognostic value of serum human epididymis protein 4 (HE4) in UCC. Pre-treatment serum samples from 109 UCC patients and 99 healthy women were analyzed for HE4 levels by a quantitative chemiluminescent microparticle immunoassay on the automated ARCHITECT instrument. HE4 serum (sHE4) levels were significantly higher in UCC patients, regardless of tumor stage, compared with healthy controls. Elevated sHE4 levels were significantly associated with advanced FIGO stage and absence of disease-free interval after treatment. In univariable analysis, higher sHE4 levels were significantly correlated with shorter overall survival and progression-free survival. In multivariable analysis, sHE4 retained its significance as independent adverse prognostic factor for both survival endpoints. This study indicates that sHE4 is associated with a more aggressive tumor phenotype and a worse patient's prognosis. These results suggest the potential role of sHE4 as a novel prognostic marker and as an indicator of high-risk UCC patients for a tailored surgical and adjuvant therapy.

Keywords: HE4; biomarker; prognosis; serum; uterine cervical carcinoma.