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Background: To explore the beneficial subgroups after radiotherapy in high-grade neuroendocrine cervical cancer (HGNECC) and construct two survival prognosis models to quantify the efficacy of radiotherapy assessment., Methods: In this retrospective study, we included 592 eligible samples from the Surveillance, Epidemiology, and End Results (SEER) database and 56 patients with lymph-node positive HGNECC from Chongqing Medical University. Cox regression analysis was used to identify independent survival prognosis risk factors for HGNECC patients. Propensity score matching (PSM) was employed as it balances the baseline differences among grouping methods. Kaplan-Meier (K-M) curves were used to analyze survival differences among different groups. Two survival prediction nomograms were constructed separately (using the "rms" package in R software) based on whether radiotherapy was administered. The stability and accuracy of these models were assessed using receiver operating characteristic (ROC) curves and calibration curves in both the training and validation datasets. P<0.05 was considered to indicate statistically significant differences., Results: Age, Federation of Gynecology and Obstetrics (FIGO)-stage, and treatment methods (surgery vs. chemotherapy) were independent risk factors that affected survival prognosis (P<0.05). Radiotherapy showed adverse effects on survival in patients with early tumor staging, lymph-node negative status, and absence of distant metastasis (all P<0.05). The lymph-node positive group had a beneficial response to radiotherapy (P<0.05), and patients with metastasis in the radiotherapy group showed a survival protection trend (P=0.069)., Conclusion: In HGNECC, patients with lymph-node positive status can benefit from radiotherapy in terms of survival outcomes. We constructed two survival prediction models based on whether radiotherapy was administered, thereby offering a more scientifically guided approach to clinical treatment planning by quantifying the radiotherapy efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Li, Ouyang, Tang, Cui and Yang.)

Background: Cervical cancer, one of the prevalent malignancies among females, is closely associated with human papillomavirus (HPV) infection. Homologous to the E6-AP carboxyl terminus (HECT) domain and ankyrin repeat containing E3 ubiquitin-protein ligase 1 (HACE1) plays pivotal roles in various cancers. This study aimed to elucidate the expression of HACE1 in cervical cancer and its correlation with clinical features., Methods: From The Cancer Genome Atlas Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA-CESC) and Gene Expression Omnibus (GEO, GSE6791) datasets, we obtained RNA-Seq profiles and associated clinical information. Differential gene analysis was conducted using the R "limma" package. Implications for HPV infection and the overall survival (OS) of cervical cancer were determined by performing differential expression analysis and the Cox proportional hazards regression model. Immunohistochemical analyses were used to validate the expression in cervical cancer and normal cervical tissue. Further, nomogram was constructed to predict OS in cervical cancer. Whether the model was credible was evaluated according to receiver operating characteristic (ROC) curves and concordance curves. To further evaluate the potential functions of HACE1, we conducted functional enrichment analysis. Finally, we assessed methylation levels in HPV+ and HPV- patients in the TCGA-CESC dataset., Results: Utilizing TCGA and GSE6791 datasets, we observed significant upregulation of HACE1 in cervical cancer patients, particularly linked to HPV infection. Immunohistochemical staining revealed enhanced HACE1 expression in tumor tissues. Further analysis demonstrated a significant positive correlation between elevated HACE1 and HPV-associated proteins (E1, E6, and E7). Moreover, high HACE1 expression was associated with adverse prognosis in cervical cancer patients. Multivariate Cox analysis indicated that HACE1 could serve as an independent prognostic factor. We developed a prognostic model integrating HPV subtypes, the International Federation of Gynecology and Obstetrics (FIGO) staging, and HACE1, exhibiting strong predictive efficacy for cervical cancer prognosis. Gene enrichment analysis indicated HACE1's potential involvement in multiple signaling pathways during cervical cancer progression, while the demethylation of cg03002526 in HPV-positive patients might contribute to HACE1 upregulation., Conclusions: Our study reveals that HACE1 upregulation is associated with cervical cancer, particularly in HPV-positive patients. HACE1 emerges as an independent prognostic factor, linked to unfavorable outcomes., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-23-2120/coif). The authors have no conflicts of interest to declare., (2024 Translational Cancer Research. All rights reserved.)