Investigator
Fuda Cancer Hospital
Tumor Invasion Distance Based on MRI Is a Novel Prognostic Indicator for I-IIIB Cervical Cancer Patients Treated with Radiotherapy
Aims:This study aimed to identify the prognostic value of tumor invasion distance (TID) based on MRI findings in cervical-cancer (CC) patients treated with radiotherapy (RT). Methods: A total of 218 CC patients diagnosed at Fujian Cancer Hospital from December 2018 to December 2019 were included in the study. Cox regression analyses were conducted to identify independent prognostic factors for overall survival (OS), including low 1/3 vaginal involvement, a longer TID, and RT without chemotherapy. These factors were subsequently used to construct a nomogram for individualized risk prediction. Kaplan–Meier survival analysis was employed to evaluate survival outcomes and establish a risk stratification system. The performance of the new stratification was assessed using the linear trend χ2 test, Akaike information criterion, and Harrell’s concordance index. Results: A longer TID was associated with worse 3-year OS (p < 0.001, HR: 3.42, 95% CI: 1.67–7.00). A longer TID, lower 1/3 vaginal involvement, and concurrent chemotherapy were independent prognostic survival factors for CC patients. Compared with the 2018 FIGO staging system, the new risk stratification system provided better monotonicity with a higher linear trend χ2 value (28.03 vs. 9.35), better discriminatory ability with smaller Akaike information criterion (312 vs. 331), and a greater Harrell C statistic (0.74 vs. 0.65) for predicting 3-year OS. Conclusions: This was the first study to demonstrate the prognostic value of TID in CC patients who received RT. The new risk stratification system based on TID could complement the 2018 FIGO staging system in identifying high-risk patients for more intense treatment and care. Further prospective research with larger samples is warranted to confirm the significance of TID for CC patients treated with RT.
IRF4 Enhances Radiosensitivity of Cervical Cancer by Inhibiting the PI3K/Akt/mTOR Pathway to Regulate Autophagy
ABSTRACT Interferon regulatory factor 4 (IRF4), a critical member of the IRF transcription factor family, harbors an elusive biological role in cervical cancer. Through immunohistochemical staining and immunoblotting, CCK‐8 viability assays, EdU incorporation tests, clonogenic survival experiments, flow cytometric detection, transmission electron microscopy, immunofluorescence staining and heterotopic transplantation model, we discover that IRF4 expression was markedly decreased in cervical cancer tissues and cell lines compared to normal controls. Overexpression of IRF4 suppressed proliferation, migration, and invasion in both Siha and HeLa cells, while concurrently enhancing radiosensitivity. Mechanistically, IRF4 upregulated autophagy‐related proteins (LC3, Beclin‐1) and promoted autophagosome formation, while downregulating P62 by inhibiting the PI3K/Akt/mTOR pathway. In vivo studies demonstrated that IRF4 augmented the tumor response to radiation and further potentiated the effects when combined with rapamycin treatment, confirming its pivotal role in promoting radiosensitivity through PI3K/Akt/mTOR‐mediated autophagy. IRF4 emerges as a critical regulator of cervical cancer progression via modulation of autophagy and influences the tumor's response to radiotherapy. It holds promise as a potential therapeutic target to enhance cervical cancer radiosensitivity.
