RESUMEN
Endometrial cancer (EC) is a highly heterogeneous malignancy characterized by varied pathology and prognoses, and the heterogeneity of its cancer cells and the tumor microenvironment (TME) remains poorly understood. We conducted single-cell RNA sequencing (scRNA-seq) on 18 EC samples, encompassing various pathological types to delineate their specific unique transcriptional landscapes. Cancer cells from diverse pathological sources displayed distinct hallmarks labeled as immune-modulating, proliferation-modulating, and metabolism-modulating cancer cells in uterine clear cell carcinomas (UCCC), well-differentiated endometrioid endometrial carcinomas (EEC-I), and uterine serous carcinomas (USC), respectively. Cancer cells from the UCCC exhibited the greatest heterogeneity. We also identified potential effective drugs and confirmed their effectiveness using patient-derived EC organoids for each pathological group. Regarding the TME, we observed that prognostically favorable CD8+ Tcyto and NK cells were prominent in normal endometrium, whereas CD4+ Treg, CD4+ Tex, and CD8+ Tex cells dominated the tumors. CXCL3+ macrophages associated with M2 signature and angiogenesis were exclusively found in tumors. Prognostically relevant epithelium-specific cancer-associated fibroblasts (eCAFs) and SOD2+ inflammatory CAFs (iCAFs) predominated in EEC-I and UCCC groups, respectively. We also validated the oncogenic effects of SOD2+ iCAFs in vitro. Our comprehensive study has yielded deeper insights into the pathogenesis of EC, potentially facilitating personalized treatments for its varied pathological types.
Asunto(s)
Neoplasias Endometriales , Análisis de la Célula Individual , Transcriptoma , Microambiente Tumoral , Humanos , Femenino , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Neoplasias Endometriales/metabolismo , Transcriptoma/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
PURPOSE: The aim of this study was to investigate whether young patients with endometrial carcinoma can preserve adnexa and lymph nodes to improve their quality of life without compromising their prognosis. METHODS: A total of 319 patients with type I endometrial carcinoma (high or moderate differentiation and less than 1/2 myometrial invasion) hospitalized in the First Affiliated Hospital of Zhengzhou University from May 2012 to July 2021 were included. The patients were divided into four groups: high differentiation without myometrial invasion group (G1MI-), high differentiation with superficial myometrial invasion group (G1MI+), moderate differentiation without myometrial invasion group (G2MI-), and moderate differentiation with superficial myometrial invasion group (G2MI+). Logistic regression analysis was conducted to identify risk factors for extra-uterine involvement. Kaplan-Meier method was used to draw the survival curve to compare the prognosis in subgroups and rates of extra-uterine involvement were also compared using Chi-square test or Fisher's exact test. RESULTS: Multivariable logistic regression revealed that differentiation (HR = 14.590, 95%CI = 1.778-119.754, p = 0.013) and myometrial invasion (HR = 10.732, 95%CI = 0.912-92.780, p = 0.037) were the independent risk factors for extra-uterine involvement. The overall difference was statistically significant (p < 0.001). In the subgroups analysis, both adnexal metastasis and lymph node metastasis were statistically significant in the G2MI+ group compared with G1MI- (p = 0.007, p = 0.008). There were no significant differences in the overall survival (OS) rate and progression free survival (PFS) rate among the four subgroups (p > 0.05). CONCLUSIONS: Surgery with adnexal preservation and without systematic lymphadenectomy could be employed for the patients who are high differentiation with less than 1/2 myometrial invasion or moderate differentiation without myometrial invasion, but not recommended to the patients with moderate differentiation and superficial myometrial invasion.
Asunto(s)
Neoplasias Endometriales , Miometrio , Invasividad Neoplásica , Humanos , Femenino , Neoplasias Endometriales/patología , Neoplasias Endometriales/mortalidad , Miometrio/patología , Pronóstico , Persona de Mediana Edad , Adulto , Medición de Riesgo , Factores de Riesgo , Diferenciación Celular , Metástasis Linfática/patologíaRESUMEN
PURPOSE: The aim of this study was to evaluate the risk factors for pelvic lymph node metastasis (LNM) and para-aortic LNM in non-endometrioid endometrial cancer (non-EEC). METHODS: A total of 283 patients with non-EEC hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2020 were included. Various characteristics were retrospectively analyzed in relation to LNM. RESULTS: Univariable and multivariable logistic regression analysis revealed cervical stromal invasion (OR = 3.441, 95% CI = 1.558-7.6, p = 0.002), myometrial invasion ≥1/2 (OR = 2.661, 95% CI = 1.327-5.337, p < 0.006), lymphovascular space involvement (LVSI) (OR = 4.118, 95% CI = 1.919-8.837, p < 0.001), positive peritoneal cytology (OR = 2.962, 95% CI = 1.344-6.530, p = 0.007), CA125 (OR = 1.002, 95% CI = 1-1.004, p = 0.026) were the independent risk factors for pelvic LNM. And myometrial invasion ≥1/2 (OR = 5.881, 95% CI = 2.056-16.427, p = 0.001), LVSI (OR = 4.962, 95% CI = 1.933-12.740, p = 0.001), adnexal (OR = 5.921, 95% CI = 2.003-17.502, p = 0.001) were the independent risk factors for para-aortic LNM. With the increase of independent risk factors, the rates of LNM were increased significantly. CONCLUSIONS: Cervical stromal invasion, myometrial invasion ≥1/2, LVSI, positive peritoneal cytology, and CA125 were risk factors for pelvic LNM. Myometrial invasion ≥1/2, LVSI and involvement of the adnexa were risk factors for para-aortic LNM which could provide a good basis to help predict which non-EEC patients are at higher risk for LNM.
Asunto(s)
Neoplasias Endometriales , Escisión del Ganglio Linfático , Femenino , Humanos , Metástasis Linfática/patología , Estudios Retrospectivos , Neoplasias Endometriales/patología , Ganglios Linfáticos/patología , Factores de Riesgo , Estadificación de Neoplasias , Invasividad Neoplásica/patologíaRESUMEN
PURPOSE: Endometrial cancer arising in adenomyosis (EC-AIA) is frequently detected accidentally following a general hysterectomy for adenomyosis. Whether supplemental lymphadenectomy in patients with EC-AIA can improve the survival outcome remains inconclusive. Herein, the authors summarized the data of patients with EC-AIA and further explored the impact of lymphadenectomy on the prognosis of these patients. METHODS: Five electronic databases, namely MEDLINE, Web of Science, PubMed, Embase, and the Cochrane Library were employed for searching articles from inception to May 2023. RESULTS: In total, 38 eligible studies enrolling 56 patients were included. Of these, 44 patients had a traceable prognosis. Kaplan-Meier curves demonstrated that patients who had undergone lymphadenectomy had a better progression-free survival (PFS) compared with those who had not undergone lymphadenectomy ( P =0.016), but there was no difference in overall survival. Univariable ( P =0.025, HR=0.25, 95% CI=0.08-0.84) and multivariable ( P =0.042, HR=0.13, 95% CI=0.020-0.930) Cox regression analyses revealed that lymphadenectomy was an independent protective factor for PFS. CONCLUSION: For patients diagnosed with EC-AIA following hysterectomy for benign disease, further supplementary lymphadenectomy is recommended to improve PFS.
Asunto(s)
Adenomiosis , Neoplasias Endometriales , Histerectomía , Escisión del Ganglio Linfático , Humanos , Femenino , Neoplasias Endometriales/cirugía , Neoplasias Endometriales/patología , Neoplasias Endometriales/mortalidad , Adenomiosis/cirugía , Adenomiosis/complicaciones , PronósticoRESUMEN
PURPOSE: CUDC-907 is a promising dual-target inhibitor of the HDAC and PI3K signaling pathways, with demonstrated therapeutic effects in a range of malignant tumors. However, its potential application in ovarian cancer (OC) has not been fully explored yet. In this study, we sought to investigate the efficacy of CUDC-907 in treating OC, both in vitro and in vivo. METHODS: Here, we examined the correlation between PI3K or HDAC expression and the prognosis of OC patients using the GEPIA database. RNA-Seq analysis was performed on OC cells treated with CUDC-907.To assess various cellular processes, including proliferation, migration, invasion, apoptosis, and cell cycle, we performed a series of assays, including the CCK8, EDU, wound healing, cell invasion, and flow cytometry assays. Real-time quantitative PCR and western blotting were performed to measure the expressions of target genes. Additionally, we utilized the SKOV3 xenograft tumor model to investigate the inhibitory effects of CUDC-907 on tumor growth in vivo. RESULTS: Bioinformatics analyses revealed that up-regulated HDAC and PI3K were significantly correlated with patients' poor survival in OC. In vivo and in vitro experiments have demonstrated that CUDC-907 could inhibit the proliferation of OC cells by inhibiting the PI3K and HDAC pathways to down-regulate the expression of c-Myc, and induce cell apoptosis by inhibiting the PI3K/AKT/Bcl-2 pathway, and up-regulate p21 to induce G2 /M phase arrest. CONCLUSION: Our results showed that CUDC-907 had powerful anti-tumor effects on OC, which could provide a theoretical and experimental basis for the application of CUDC-907 in the therapy of OC.
Asunto(s)
Morfolinas , Neoplasias Ováricas , Fosfatidilinositol 3-Quinasas , Pirimidinas , Humanos , Femenino , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de Histona Desacetilasas/farmacología , Línea Celular Tumoral , Proliferación Celular , Neoplasias Ováricas/tratamiento farmacológico , ApoptosisRESUMEN
BACKGROUND: Endometrial carcinoma (EC) is the second most common gynecological malignancy, and the differences between different pathological types are not entirely clear. Here, we retrospectively collected eligible EC patients to explore their differences regarding clinical characteristics and prognosis. METHODS: Five hundred seventy EC patients from the First Affiliated Hospital of Zhengzhou University were included. Prognostic factors were measured using the univariate/multivariate Cox models. Overall survival (OS) and progression-free survival (PFS) were the primary and secondary endpoints, respectively. RESULTS: In total, 396 patients with uterine endometrioid carcinoma (UEC), 106 patients with uterine serous carcinoma (USC), 34 patients with uterine mixed carcinoma (UMC), and 34 patients with uterine clear cell carcinoma (UCCC) were included. Comparison of baseline characteristics revealed patients diagnosed with UEC were younger, had more early clinical stage, and had lower incidence of menopause and lymph node metastasis. Compared to UEC, other pathological EC obtained more unfavorable OS (UCCC: HR = 12.944, 95%CI = 4.231-39.599, P < 0.001; USC: HR = 5.958, 95%CI = 2.404-14.765, P < 0.001; UMC: HR = 1.777, 95%CI = 0.209-15.114, P = 0.599) and PFS (UCCC: HR = 8.696, 95%CI = 1.972-38.354, P = 0.004; USC: HR = 4.131, 95%CI = 1.243-13.729, P = 0.021; UMC: HR = 5.356, 95%CI = 0.935-30.692, P = 0.060). Compared with UEC patients, the OS of UCCC patients in stage I-II and USC patients in stage III-IV were significantly worse, while UMC patients in stage I-II favored poorer PFS. The OS of UCCC patients receiving no postoperative adjuvant therapy or chemotherapy alone were significantly worse. CONCLUSIONS: The baseline characteristics of UEC and other rare EC types varied greatly, and the prognostic significance of different pathological types on EC patients depended on clinical tumor stages and therapeutic options.
Asunto(s)
Carcinoma , Neoplasias Endometriales , Neoplasias Uterinas , Femenino , Humanos , Estudios Retrospectivos , Estadificación de Neoplasias , Pronóstico , Neoplasias Endometriales/terapia , Neoplasias Endometriales/patología , Neoplasias Uterinas/patología , Carcinoma/patologíaRESUMEN
OBJECTIVES: To explore the differences in clinical characteristics, prognosis, and risk factors between type I and type II endometrial cancer (EC). MATERIALS AND METHODS: We retrospectively collected EC patients diagnosed with type I or type II EC from 2009 to 2021 in the First Affiliated Hospital of Zhengzhou University. RESULTS: In total, 606 eligible EC patients (396 type I, and 210 type II) were included. Baseline analyses revealed that type II patients were older, had more advanced clinical stage, were more likely to receive chemoradiotherapy, and had higher incidence of myometrial infiltration, cervix involvement, lymph node metastasis and positive ascites cytology. Type II significantly favored poorer overall survival (OS) (HR = 9.10, 95%CI 4.79-17.28, P < 0.001) and progression-free survival (PFS) (HR = 6.07, 95%CI 2.75-13.37, P < 0.001) compared to type I. For all included EC, univariate and multivariate COX analyses revealed age, myometrial infiltration and pathological type were independent risk factors for OS and PFS. Subgroup analyses identified age, menopause, clinical stage, and lymph node metastasis as independent risk factors for type I regarding OS. While age, myometrial infiltration and chemoradiotherapy were identified as risk and protective factors for type II regrading OS. Age and cervix involvement were identified as independent risk factors for type I regarding PFS. Myometrial infiltration was identified as independent risk factor for type II regarding PFS. CONCLUSION: Type II patients shared different clinical characteristics and worse prognosis compared to type I, and their independent risk and protective factors also varied.
RESUMEN
OBJECTIVE: This study aimed to compare the survival outcome of 3 different treatment groups (arterial interventional chemotherapy or intravenous chemotherapy or concurrent chemoradiotherapy) for locally advanced cervical cancer. METHODS: A total of 187 patients with pathological stage IB3-IIB cervical cancer (cervical squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma) hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2013 to May 2019 were included. Therefore, this article is a retrospective study. We collected data from all eligible patients. And all according to the treatment methods at that time, they were divided into three subgroups: (1) 40 patients who received neoadjuvant arterial interventional chemotherapy + surgery + postoperative chemotherapy (IA-NAC + RS), (2) 63 patients who received neoadjuvant intravenous chemotherapy + surgery + postoperative chemotherapy (IV-NAC + RS), (3) 84 patients who only received concurrent chemoradiotherapy (CCRT). Notably, 108 of these patients met the 5-year follow-up period, and 187 patients met the 3-year follow-up period only. Consequently, we compared 5-year survival and 3-year survival separately. The prognosis (5-year survival and 3-year survival) of the three groups and the chemotherapy efficacy, intraoperative blood loss, operation time, and postoperative pathological risk factors of different subgroups were compared. RESULTS: (1) There were no significant differences in the 3-year overall survival (OS) rate, 3-year progression-free survival (PFS) rate, 5-year OS rate, and 5-year PFS rate among the three subgroups (p > 0.05). (2) The chemotherapy response rates of IA-NAC+RS group (37.5%) and IV-NAC+RS group (25.4%) were comparable (p > 0.05). (3) The intraoperative blood loss in the IA-NAC+RS group (average 92.13±84.09 mL) was significantly lower than that in the IV-NAC+RS group (average 127.2±82.36 mL) (p < 0.05). (4) The operation time of the IA-NAC+RS group (average 231.43±63.10 min) and the IV-NAC+RS group (average 219.82±49.11 min) were comparable (p > 0.05). (5) There were no significant differences between the IA-NAC+RS group and IV-NAC+RS group in pathological lymph node metastasis, parametrial invasion, and involvement of lymphovascular space (p > 0.05). CONCLUSIONS: Neoadjuvant chemotherapy combined with surgery had the same long-term survival benefit as concurrent chemoradiotherapy.