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Objective@#Aimed to construct an immune-related risk signature and nomogram predicting endometrial cancer (EC) prognosis. @*Methods@#An immune-related risk signature in EC was constructed using the least absolute shrinkage and selection operator regression analysis based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A nomogram integrating the immune-related genes and the clinicopathological characteristics was established and validated using the Kaplan-Meier survival curve and receiver operating characteristic (ROC) curve to predict the overall survival (OS) of EC patients. The Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) R tool was used to explore the immune and stromal scores. @*Results@#CCL17, CTLA4, GPI, HDGF, HFE2, ICOS, IFNG, IL21R, KAL1, NR3C1, S100A2, and S100A9 were used in developing an immune-related risk signature evaluation model. The Kaplan-Meier curve indicated that patients in the low-risk group had better OS (p<0.001).The area under the ROC curve (AUC) values of this model were 0.737, 0.764, and 0.782 for the 3-, 5-, and 7-year OS, respectively. A nomogram integrating the immune-related risk model and clinical features could accurately predict the OS (AUC=0.772, 0.786, and 0.817 at 3-, 5-, and 7-year OS, respectively). The 4 immune cell scores were lower in the high-risk group. Forkhead box P3 (FOXP3) and basic leucine zipper ATF-like transcription factor (BATF) showed a potential significant role in the immune-related risk signature. @*Conclusion@#Twelve immune-related genes signature and nomogram for assessing the OS of patients with EC had a good practical value.
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Objective:To explore the application and clinical significance of the cancer genome atlas (TCGA) molecular classification in endometrial cancer (EC).Methods:Sixty-six EC patients collected from December 2018 to March 2021 from Peking University People′s Hospital were categorized into four subgroups based on TCGA molecular classification tested by next generation sequencing. The correlation among four molecular subgroups and the clinical-pathological features including prognosis were analyzed.Results:(1) Clinical and pathological features: median age at diagnosis was 56 years (range: 24-78 years). The cases were distributed as follows: 3 (5%) cases DNA polymerase epsilon (POLE) ultra-mutated, 11 (17%) cases high microsatellite instability (MSI-H) including 2 Lynch syndrome, 42 (64%) cases low copy-number (CN-L) and 10 (15%) cases high copy-number (CN-H). There were significant differences among four subtypes in the combination of other tumors, tumor family history, surgical method, International Federation of Gynecology and Obstetrics (FIGO, 2009) stage, depth of muscle invasion and lymph vascular space invasion (all P<0.05). The proportions of patients in CN-H subgroup with advanced FIGO stage (stage Ⅲ-Ⅳ), deep muscle invasion and positive lymph-vascular space invasion were significantly increased. There were no significant differences in age, menopausal status, body mass index, metabolic syndrome-related complications, preoperative serum CA 125 and human epididymis protein 4 levels, tumor size, pathological grade (only endometrioid cancer), and lymph node metastasis among the 4 TCGA molecular types (all P>0.05). (2) Immuno-related molecular analysis: among 66 EC patients, 27 patients underwent immunohistochemical analysis of programmed cell death 1 ligand 1 (PD-L1) protein, and 28 patients underwent tumor mutation burden (TMB) detection. POLE and MSI-H subgroups contained TMB than those in CN-L and CN-H ( P<0.05).(3) Prognosis: the median follow-up time was 10 months (range: 0-28 months). The progression-free survival rate of TCGA molecular types were 100% (POLE ultra-mutated), 100% (MSI-H), 98% (CN-L), and 80% (CN-H) respectively and had significant differences ( P=0.034). The overall survival were 100% (POLE ultra-mutated), 100% (MSI-H), 98% (CN-L), and 90% (CN-H) respectively, but there were not statistically significant difference ( P=0.361). POLE ultra-mutated and MSI-H subgroups had the best survival, while CN-H had the worst. Conclusion:TCGA molecular classification has feasibility and clinical value in clinical application of EC, which is helpful to identify the prognosis of patients.
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Objective:To investigate the clinical significance of the primary tumor size in patients with endometrial carcinoma (EC).Methods:A total of 385 patients with EC admitted to Peking University People's Hospital from January 2006 to December 2016 with complete follow up data were selected, whose tumor size data before biopsy were retrospectively studied.Results:(1) The mean diameter of the primary tumor was (3.6±1.8) cm (range: 1-15 cm). And 48 cases were 0-<2 cm, 78 cases were 2-<3 cm, 92 cases were 3-<4 cm, 73 cases were 4-<5 cm, 94 cases were ≥5 cm. The diameter of the tumor was associated with age <60 years old, premenopause, CA 125≥35 kU/L, non-parturition, poor differentiation, stage Ⅲ-Ⅳ, depth of myometrial infiltration ≥1/2, cervical interstitial involvement, adnexal metastasis and lymph node metastasis (all P<0.05), but not associated with body mass index, hypertension, diabetes mellitus, pathology, lymph-vascular space invasion (all P>0.05). (2) Among the 334 patients underwent lymphadenectomy, 45 (13.5%, 45/334) cases with lymph node metastasis were observed. Stratified analysis showed that lymph node metastasis and recurrence rate of patients with EC gradually increased with the increase of tumor size ( P<0.05). Adopting 2, 3, 4 and 5 cm as cut-off values of tumor size, there were significant differences in the rate of lymph node metastasis and recurrence among them observed ( P<0.05), except for lymph node metastasis rate and recurrence rate when the cut-off value was 2 cm ( P>0.05). (3) An receiver operating characteristic (ROC) curve analysis showed that a tumor diameter of 4.25 cm was the cut-off prognostic value to predict lymph node metastasis and recurrence of EC. Conclusions:Tumor diameter is significantly correlated with lymph node metastasis and recurrence in patients with EC. Tumor size should be considered in determining the scope of surgery and adjuvant therapy.
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Objective@#This study aims to analyze factors associated with lymphovascular space invasion (LVSI) and evaluate the prognostic significance of LVSI in Chinese endometrioid endometrial cancer (EEC) patients. @*Methods@#Five-hundred eighty-four EEC patients undergoing surgery in our center from 2006 to 2016 were selected for analysis. Univariate analysis and multivariate logistic regression were used to examine relevant factors of LVSI. To evaluate the prognostic role of LVSI, survival analyses were conducted. In survival analyses, both multivariate Cox regression and propensity score matching were used to control the confounders. @*Results@#The incidence of LVSI was 12.16% (71/584). Diabetes history (p=0.021), lymph node metastasis (p=0.005), deep myometrial invasion (p<0.001) and negative PR expression (p=0.007) were independently associated with LVSI. Both Kaplan-Meier method and univariate Cox regressions showed LVSI negative and positive cases had similar tumor-specific survival (TSS) and disease-free survival (DFS). After adjusting for the influence of adjuvant therapy and other clinicopathological factors with multivariate Cox regressions, LVSI still could not bring additional survival risk to the patients (p=0.280 and p=0.650 for TSS and DFS, respectively). This result was verified by Kaplan-Meier survival analyses after propensity score matching (p=0.234 and p=0.765 for TSS and DFS, respectively). @*Conclusion@#LVSI does not significantly compromise the survival outcome of Chinese EEC patients.