Zhu J, et al. J Gynecol Oncol. 2017 Jul;28(6):e77. https://doi.org/10.3802/jgo.2017.28.e77

Zhu J, et al. J Gynecol Oncol. 2015 Dec;27(2):e18. https://doi.org/10.3802/jgo.2016.27.e18

Background: Metastasis is a major obstacle in the treatment of cervical cancer (CC), and SPOP-mediated regulatory effects are involved in metastasis. However, the mechanisms have not been fully elucidated. Methods: Proteomic sequencing and SPOP immunohistochemistry (IHC) were performed for the pelvic lymph node (pLN)-positive and non-pLN groups of CC patients. The corresponding patients were stratified by SPOP expression level for overall survival (OS) and relapse-free survival (RFS) analysis. In vitro and in vivo tests were conducted to verify the causal relationship between SPOP expression and CC metastasis. Multiplex immunofluorescence (m-IF) and the HALO system were used to analyse the mechanism, which was further verified by in vitro experiments. Results: SPOP is upregulated in CC with pLN metastasis and negatively associated with patient outcome. In vitro and in vivo, SPOP promotes CC proliferation and metastasis. According to m-IF and HALO analysis, SPOP may promote CC metastasis by promoting the separation of PD-1 from PD-L1. Finally, it was further verified that SPOP can achieve immune tolerance by promoting the movement of PD-1 away from PD-L1 in spatial location and function. Conclusion: This study shows that SPOP can inhibit the immune microenvironment by promoting the movement of PD-1 away from PD-L1, thereby promoting pLN metastasis of CC and resulting in worse OS and RFS.

Kobayashi Y, et al. J Gynecol Oncol. 2024 Apr;35:e87. https://doi.org/10.3802/jgo.2024.35.e87

Objective: There is a lack of research evaluating the effect of tumor markers for prognosis in cervical adenocarcinoma. We aimed to develop and validate a preoperative tumor-marker-based model including clinicopathological factors to clarify the prognostic value of endocervical adenocarcinoma. Methods: A total of 572 patients with cervical adenocarcinoma who were staged at the International Federation of Gynecology and Obstetrics (FIGO) IA–IIA were reviewed retrospectively. Preoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA)-125 and CA19-9 levels were measured. The survival and recurrence patterns were analyzed according to the tumor-marker-related stratification. The predictive values of biomarkers and clinical variables were assessed with Cox regression and competing risk models. Results: Patients with elevated preoperative tumor markers had evidently poor overall survival and recurrence-free survival. The triple-elevated tumor marker (TETM) subgroup had the worst overall survival and progression-free survival than the triple-negative tumor marker (TNTM) subgroup and the single-elevated tumor marker (SETM) subgroup. The most important predictors for overall survival were elevated tumor markers, FIGO-stage, tumor differentiation, lymphovascular space invasion (LVSI) and lymph nodes metastasis. The most important predictors for recurrence-free survival were elevated tumor markers, FIGO-stage, tumor differentiation, LVSI and deep stromal invasion. Stratified analysis showed that elevated CA-125 and CA19-9 were significantly associated with postoperative distant metastasis. A decision curve analysis confirmed that a combination of tumor markers as predictors significantly outperformed the other common predictors used (FIGO-stage, intermediate and high-risk factors, tumor differentiation, lymph nodes). Conclusions: Elevated preoperative serum CEA, CA-125, and CA19-9 levels exhibited poor overall survival and recurrence-free survival in cervical adenocarcinoma patients. Combined preoperative serum CA-125 and CA19-9 independently predicted distant metastasis in patients with endocervical adenocarcinoma.