Epithelial–mesenchymal transition, proliferation, and angiogenesis in locally advanced cervical cancer treated with chemoradiotherapy

Abstract

We evaluated the association between epithelial–mesenchymal transition (EMT)‐derived markers and expression of proteins associated with cell proliferation and tumor growth, as well as their prognostic roles, in 61 patients (mean age 52 ± 10 years) with locally advanced cervical cancer, all of whom were treated with chemoradiation and intracavitary brachytherapy. We used immunohistochemical analysis to assess the expression of proteins targeted in our investigation. Various statistical analyses were then conducted to assess protein marker associations with survival outcomes. Forty‐six percent of the patients were positive for human papilloma virus. Median progression‐free survival (PFS) was 6.6 months (95% confidence interval [CI]: 4.0–9.1, whereas overall survival (OS) was 30.0 months (95% CI: 11–48). Multivariate analysis demonstrated that vascular endothelial growth factor (VEGF) (P = 0.002), epidermal growth factor receptor (EGFR) (P = 0.001), and TWIST2 (P = 0.001) expression levels, as well as a tumor size <6 cm (P = 0.02), influenced OS. Changes in TWIST2 levels and loss of E‐cadherin expression were correlated with VEGF and EGFR levels; furthermore, patients with high TWIST2 expression had shorter OS (P = 0.0001), as those with loss of E‐cadherin (P = 0.02). OS was even shorter when positive EGFR or VEGF expression was related with EMT markers (positive EGFR + negative E‐cadherin: median 14 months, 95% CI: 3–24; negative EGFR + positive E‐cadherin: median 31 months, 95% CI: 14–NA; P = 0.02.). The presence of EMT markers was associated with proliferative and pro‐angiogenic protein expression and influenced the prognosis of locally advanced cervical cancer.

Thymoquinone Inhibits the Migration and Invasive Characteristics of Cervical Cancer Cells SiHa and CaSki In Vitro by Targeting Epithelial to Mesenchymal Transition Associated Transcription Factors Twist1 and Zeb1

“…Studies revealed that abnormal expression of EMT-TFs are associated with metastatic process [ 9 , 17 ]. Cervical cancer, which is the second most common gynecological malignant tumor in females worldwide, has a high morbidity in China, and resistance to chemotherapy is a major obstacle for effective treatment of cancers, including cervical cancer [ 23 , 24 ]. The acquisition of EMT features has been proposed as the key contributor of chemoresistance in cancer cells.…”

Prognostic value of the pretreatment neutrophil-to-lymphocyte ratio in cervical cancer: a meta-analysis and systematic review

“…All of these factors have been documented to be the powerful variables related to CC progression and compromise long-term survival [39–42]. Herein, high NLR is closely associated with more aggressive tumor behavior which is contributed to shorter OS and PFS.…”

Systems Biology of Cancer Metastasis

“…In the absence of a longitudinal sampling strategy, coupling information at the genomic or transcriptomic level with experimental measurements of cell phenotype may provide guidance to the level of granularity required when interpreting single time point data. Techniques that can accurately quantify, at the single-cell level, a physical characteristic, such as a change in cell mass or modulation of cell motility due to drug treatment or an environmental perturbation, could provide the additional data required to differentiate between a stable and transient cell state when coupled with single-cell molecular data (Rojas-Puentes et al, 2016). Even when longitudinal data is available, the integration of multiple data types, such as bulk and single-cell whole-genome sequencing and transcriptomic profiling may be required to predict an outcome with accuracy (Brady et al, 2017).…”