TY - JOUR
T1 - Identifying Molecular Changes in Early Cervical Cancer Samples of Patients That Developed Metastasis
AU - de Geus, Vera
AU - Ewing-Graham, Patricia C.
AU - de Koning, Willem
AU - de Koning, Maurits N.C.
AU - van den Bosch, Thierry P.P.
AU - Nigg, Alex L.
AU - van Eijck, Casper H.J.
AU - Jozwiak, Marta
AU - van Beekhuizen, Heleen J.
AU - Mustafa, Dana A.M.
N1 - Funding Information:
This work was supported by generous contributions to the Erasmus Trustfonds (Hoijerik fund) and by the Support Casper Foundation (www.supportcasper.org).
Publisher Copyright:
Copyright © 2022 de Geus, Ewing-Graham, de Koning, de Koning, van den Bosch, Nigg, van Eijck, Jozwiak, van Beekhuizen and Mustafa.
PY - 2022/1/11
Y1 - 2022/1/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85123413988&partnerID=8YFLogxK
U2 - 10.3389/fonc.2021.715077
DO - 10.3389/fonc.2021.715077
M3 - Article
C2 - 35087740
AN - SCOPUS:85123413988
SN - 2234-943X
VL - 11
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 715077
ER -