Identifying Molecular Changes in Early Cervical Cancer Samples of Patients That Developed Metastasis

Vera de Geus; Patricia C Ewing-Graham; Willem de Koning; Maurits N C de Koning; Thierry P P van den Bosch; Alex L Nigg; Casper H J van Eijck; Marta Jozwiak; Heleen J van Beekhuizen; Dana A M Mustafa

doi:10.3389/fonc.2021.715077

Identifying Molecular Changes in Early Cervical Cancer Samples of Patients That Developed Metastasis

Front Oncol. 2022 Jan 11:11:715077. doi: 10.3389/fonc.2021.715077. eCollection 2021.

Affiliations

¹ Department of Gynaecologic Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands.
² Department of Pathology, Tumor Immuno-Pathology Laboratory, Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands.
³ Department of Pathology, Erasmus MC Cancer Institute, Rotterdam, Netherlands.
⁴ Department of Pathology, Clinical Bioinformatics Unit, Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands.
⁵ Department of Research & Development Services, Delft Diagnostic Laboratory (DDL) Diagnostic Laboratory, Rijswijk, Netherlands.
⁶ Department of Surgery, Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands.

Abstract

Cervical cancer is one of the most common cancers in women worldwide. Patients diagnosed with early-stage cervical cancer have a good prognosis, however, 10-20% suffer from local or distant recurrent disease after primary treatment. Treatment options for recurrent cervical cancer are limited. Therefore, it is crucial to identify factors that can predict patients with an increased risk of recurrence to optimize treatment to prevent the recurrence of cervical cancer. We aimed to identify biomarkers in early-stage primary cervical cancer which recurred after surgery. Formalin-Fixed, Paraffin-Embedded surgical specimens of 34 patients with early-stage cervical cancer (FIGO 2009 stage 1B1) and 7 healthy controls were analyzed. Targeted gene expression profiling using the PanCancer IO 360 panel of NanoString Technology was performed. The findings were confirmed by performing immunohistochemistry stainings. Various genes, namely GLS, CD36, WNT5a, HRAS, DDB2, PIK3R2, and CDH2 were found to be differentially highly expressed in primary cervical cancer samples of patients who developed distant recurrence. In addition, The relative infiltration score of CD8+ T cells, CD80+CD86+ macrophages, CD163+MRC1+ macrophages, and FOXP3+IL2RA+ regulatory T cells were significantly higher in this group of samples. In contrast, no significant differences in gene expression and relative immune infiltration were found in samples of patients who developed local recurrence. The infiltration of CD8 and FOXP3 cells were validated by immunohistochemistry using all samples included in the study. We identified molecular alterations in primary cervical cancer samples from patients who developed recurrent disease. These findings can be utilized towards developing a molecular signature for the early detection of patients with a high risk to develop metastasis.

Keywords: cancer-related genes; distant recurrence; early-stage cervical cancer; immune microenvironment; local recurrence.