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1.
J Ovarian Res ; 17(1): 85, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38641834

RESUMO

BACKGROUND: Omentectomy is an important procedure in surgery for epithelial ovarian cancer, but the scope of omentectomy is not recommended in the guidelines. This study was performed to evaluate the benefits and risks of infragastric omentectomy in patients with epithelial ovarian cancer. METHODS: This trial is a single center prospective study. Primary epithelial ovarian cancer patients with normal-appearing omentum were randomly assigned to either the control or experimental group and underwent infracolic or infragastric omentectomy, respectively. The primary endpoint was progression-free survival. This trial is registered on Chinese clinical trial registry site (ChiCTR1800018771). RESULTS: A total of 106 patients meeting the inclusion criteria for ovarian cancer were included during the study period. Of these, 53 patients underwent infracolic omentectomy, whereas 53 patients received infragastric omentectomy. Multivariate analysis revealed that infragastric omentectomy could improve the detection rate of omental metastases (OR: 6.519, P = 0.005). Infragastric omentectomy improved progression-free survival significantly for those cases with higher than stage IIB disease (HR: 0.456, P = 0.041). Based on the short-term results, infragastric omentectomy did not cause more perioperative complications. CONCLUSIONS: Compared with infracolic omentectomy, infragrastric omentectomy may be a more appropriate surgical procedure for stage IIB-IIIC epithelial ovarian cancer patients with normal-appearing omentum.


Assuntos
Omento , Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/cirurgia , Carcinoma Epitelial do Ovário/patologia , Omento/cirurgia , Omento/patologia , Procedimentos Cirúrgicos de Citorredução , Estudos Prospectivos , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia
2.
J Ovarian Res ; 17(1): 61, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486335

RESUMO

BACKGROUND: Lymph node metastasis (LNM) is a major factor contributing to the high mortality rate of ovarian cancer, making the treatment of this disease challenging. However, the molecular mechanism underlying LNM in ovarian cancer is still not well understood, posing a significant obstacle to overcome. RESULTS: Through data mining from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we have identified MEOX1 as a specific gene associated with LNM in ovarian cancer. The expression of MEOX1 was found to be relatively high in serous ovarian adenocarcinoma, and its higher expression were associated with increased tumor grade and poorer clinical prognosis for ovarian cancer patients. Bioinformatics analysis revealed that MEOX1 exhibited the highest mRNA levels among all cancer types in ovarian cancer tissues and cell lines. Furthermore, gene set enrichment analysis (GSEA) and pathway analysis demonstrated that MEOX1 was involved in various LNM-related biological activities, such as lymphangiogenesis, lymphatic vessel formation during metastasis, epithelial-mesenchymal transition (EMT), G2/M checkpoint, degradation of extracellular matrix, and collagen formation. Additionally, the expression of MEOX1 was positively correlated with the expression of numerous prolymphangiogenic factors in ovarian cancer. To validate our findings, we conducted experiments using clinical tissue specimens and cell lines, which confirmed that MEOX1 was highly expressed in high-grade serous ovarian cancer (HGSOC) tissues and various ovarian cancer cell lines (A2780, SKOV3, HO8910, and OVCAR5) compared to normal ovarian tissues and normal ovarian epithelial cell line IOSE-80, respectively. Notably, we observed a higher protein level of MEOX1 in tumor tissues of LNM-positive HGSOC compared to LNM-negative HGSOC. Moreover, our fundamental experiments demonstrated that suppression of MEOX1 led to inhibitory effects on ovarian cancer cell proliferation and EMT, while overexpression of MEOX1 enhanced the proliferation and EMT capacities of ovarian cancer cells. CONCLUSIONS: The results of our study indicate that MEOX1 plays a role in the lymph node metastasis of ovarian cancer by regulating multiple biological activities, including the proliferation and EMT of ovarian cancer, lymphangiogenesis, and ECM remodeling. Our findings suggest that MEOX1 could serve as a potential biomarker for the diagnosis and treatment of ovarian cancer with LNM.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Linhagem Celular Tumoral , Metástase Linfática , Carcinoma Epitelial do Ovário , Proliferação de Células , Fatores de Transcrição/genética , Proteínas de Homeodomínio
3.
World J Surg Oncol ; 22(1): 44, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38317230

RESUMO

BACKGROUND: Epithelial ovarian cancer (EOC) is insensitive to immunotherapy due to its poor immunogenicity; thus, suitable biomarkers need to be identified for better prognostic stratification and individualized treatment. CD47 is a novel immunotherapy target; however, its impact on EOC prognosis is controversial and correlation with genetic features is unclear. The aim of this study was to investigate the prognostic significance of CD47 and its correlations with biological behaviors and genetic features of EOC. METHODS: Immunohistochemistry (IHC) and next-generation sequencing (NGS) were performed to examine expressions of CD47, PD-L1, and genomic mutations in the tissue samples of 75 EOC patients. Various clinicopathologic and genomic features were then evaluated to determine their correlation with CD47 expression. Kaplan-Meier analysis and Cox regression analysis were used to identify independent prognostic factors. Risk score modeling was then established, and the predictive capacity of this model was further confirmed by nomogram analysis. RESULTS: CD47 was mainly expressed in the tumor cell membrane and cytoplasm, and the rate of high CD47 expression was 63.7%. CD47 expression was associated with various clinicopathological factors, including FIGO stage, CA125 and HE4 value, presence of multidisciplinary surgeries, presence and volume of ascites, lymph-node metastasis, Ki-67 index and platinum-resistant, as well as genetic characteristics like BRCA mutation, HRD status, and TP53 mutation in EOC. Patients with high CD47 expression showed worse prognosis than the low-expression group. Cox regression analysis demonstrated that CA125, CD47, and BRCA mutation were independent factors for EOC prognosis. Patients were then categorized into high-risk and low-risk subgroups based on the risk score of the aforementioned independent factors, and the prognosis of the high-risk group was worse than those of the low-risk group. The nomogram showed adequate discrimination with a concordance index of 0.777 (95% CI, 0.732-0.822). The calibration curve showed good consistency. CONCLUSION: CD47 correlated with various malignant biology and genetic characteristics of EOC and may play pivotal and multifaceted roles in the tumor microenvironment of EOC Finally, we constructed a reliable prediction model centered on CD47 and integrated CA125 and BRCA to better guide high-risk population management.


Assuntos
Neoplasias Epiteliais e Glandulares , Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Prognóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Antígeno CD47/genética , Biomarcadores Tumorais/genética , Estimativa de Kaplan-Meier , Neoplasias Epiteliais e Glandulares/genética , Microambiente Tumoral
4.
Arch Gynecol Obstet ; 309(4): 1483-1490, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37695371

RESUMO

PURPOSE: To elucidate the clinicopathological features and prognostic factors of minimal deviation adenocarcinoma (MDA) of the uterine cervix, a clinically rare but highly invasive disease. METHODS: This was a retrospective, observational, real-world study of 43 patients with pathologically confirmed MDA at the Obstetrics and Gynaecology Hospital of Fudan University between November 2010 and November 2021. Baseline clinicopathological data were collected and reviewed. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were investigated by univariate and multivariate Cox proportional hazards analyses. RESULTS: Chief complaints included irregular vaginal discharge and/or bleeding (74.4%). Preoperative diagnosis was difficult, the detection rate was low (36.8%), all cases showed endophytic lesions, and 88.4% had deep stromal invasion, with biologically aggressive characteristics. The ovarian metastasis rate was high (16.3%, 7/43). The median maximum diameter of the tumour (MDOT) was 4.3 cm (range, 0.5-8.0 cm). MDOT was significantly associated with OS (P = 0.009), and the optimal cut-off value to define bulky MDA was 5.5 cm (P < 0.0001, χ= 21.161) using X-tile software. Independent prognostic factors included MDOT (HR = 10.095, P = 0.001) and ovarian metastasis (HR = 5.888, P = 0.008) for OS and MDOT (HR = 3.944, P = 0.028), ovarian metastasis (HR = 9.285, P = 0.001), and deep infiltration (HR = 3.627, P = 0.048) for PFS. CONCLUSION: Endophytic lesion development and ovarian metastasis are likely in MDA. A bulky tumour and ovarian metastasis indicate a worse prognosis. Given the special biological features of MDA, it is more appropriate to use 5.5 cm as the threshold for defining a bulky tumour than it is to use 4 cm. Ovary removal should be given higher priority to improve prognosis.


Assuntos
Adenocarcinoma , Neoplasias Ovarianas , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/cirurgia , Prognóstico , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Estudos Longitudinais , Estudos Retrospectivos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Estadiamento de Neoplasias
5.
J Cell Physiol ; 239(1): 97-111, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37921259

RESUMO

Tumor-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment, and the M2-type TAMs can promote tumor growth, invasion and angiogenesis, and suppress antitumor immune responses. It has been reported that spectrin beta, non-erythrocytic 1 (SPTBN1) may inhibit the infiltration of macrophages in Sptbn1+/-  mouse liver, but whether tumor SPTBN1 affects TAMs polarization remains unclear. This study investigated the effect and mechanism of tumor cell SPTBN1 on polarization and migration of TAMs in hepatoma and breast cancer. By analyzing tumor immune databases, we found a negative correlation between SPTBN1 and abundance of macrophages and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. By reverse transcription-quantitative real-time PCR assays and cell migration assays, the migration and M2 polarization of macrophages were enhanced by the culture medium from hepatocellular carcinoma cell line PLC/PRF/5, SNU449, and breast cancer cell line MDA-MB-231 with SPTBN1 suppression, which could be reversed by CXCL1 neutralizing antibody MAB275. Meanwhile, the ability of migration and colony formation of PLC/PRF/5, SNU449, and MDA-MB-231 cells were promoted when coculture with M2 macrophages. We also found that SPTBN1 regulated CXCL1 through p65 by cytoplasmic-nuclear protein isolation experiments and ChIP-qPCR. Our data suggest that tumor cell SPTBN1 inhibits migration and M2-type polarization of TAMs by reducing the expression and secretion of CXCL1 via inhibiting p65 nuclear localization.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Espectrina , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Neoplasias Hepáticas/metabolismo , Macrófagos/metabolismo , Microambiente Tumoral , Macrófagos Associados a Tumor/patologia , Humanos , Espectrina/metabolismo , Quimiocina CXCL1
6.
World J Surg Oncol ; 21(1): 375, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38037085

RESUMO

INTRODUCTION: To evaluate the efficacy of cytoreductive surgery versus chemotherapy for the treatment of limited regional, platinum-resistant ovarian cancer (PROC). MATERIALS AND METHODS: The clinical records of all patients with PROC treated in our center between March 2015 and March 2022 were retrospectively reviewed. We compared the oncology outcomes of patients who received cytoreduction or chemotherapy alone at relapse and presented information about postoperative adjuvant chemotherapy. RESULTS: Among 52 patients with limited regional recurrence, 40.4% (21/52) underwent cytoreduction because of platinum resistance, and 59.6% (31/52) received chemotherapy alone. No residual disease (R0) was achieved in 20 patients (95.2%). The severe morbidity rate within 30 days after the surgery was 15%. The median follow-up was 70.6 months. Compared with the chemotherapy alone group, the surgery group with R0 had better progression-free survival (PFS) (10.6 vs. 5.1 months; hazard ratio (HR) = 0.421; P = 0.0035) and post-relapse survival (PRS) (32.6 vs. 16.3 months; HR = 0.478; P = 0.047), but there was no difference in overall survival (OS) between the two groups. Laparoscopy is associated with lesser intraoperative blood loss with no differences in survival and postoperative complications compared to the open approach (P = 0.0042). Subgroup survival analysis showed that compared with chemotherapy alone, surgery prolonged PFS in patients regardless of tumor size (greater than or equal to 4 cm or less). Surgery group patients who achieved R0 had an objective response rate (ORR) of 36.8% (7/19), among whom 40% (4/10) received platinum rechallenge chemotherapy and 33.3% (3/9) were administered non-platinum chemotherapy. CONCLUSION: When well-selected PROC patients with limited regional recurrence achieved R0, their outcomes were superior to those of patients who received only chemotherapy with an acceptable morbidity rate. Laparoscope technology could be a reliable alternative surgical approach. The reintroduction of platinum agents may be considered following surgery. Further analyses in a larger population are warranted to elucidate the risks and benefits of this surgery and adjuvant chemotherapy strategy.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Procedimentos Cirúrgicos de Citorredução , Estudos Retrospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , Carcinoma Epitelial do Ovário , Recidiva
7.
Medicine (Baltimore) ; 102(38): e35169, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37746990

RESUMO

The occurrence of urinary retention is significantly higher in women undergoing forceps-assisted midwifery. However, the majority of these women typically regain the ability to urinate spontaneously within 72 hours after delivery. Instances of persistent urinary retention beyond this timeframe are relatively uncommon and have been rarely documented. This study aimed to investigate the risk factors associated with the persistence of urinary retention after forceps-assisted midwifery. A retrospective analysis was conducted on women who underwent forceps-assisted deliveries at the Obstetrics and Gynecology Hospital of Fudan University (China) between August 1, 2019 and December 1, 2019. The study involved collecting general clinical information of these women. Based on the duration of ureter retention, women who had a retention time >72 hours were categorized into group A, while those with a retention time <72 hours were allocated to group B. After performing analysis on the risk factors of persistent urinary retention following forceps delivery, the t test was utilized for analyzing single factors, while logistic regression analysis was employed for assessing multiple factors. Univariate analysis revealed a significant difference in the duration of the second stage of labor between group A and group B. However, logistic regression analysis did not indicate any significant difference between the 2 groups. Further research is still required to determine whether the association between persistent urinary retention following forceps delivery and prolonged second stage of labor is significant, considering the limited number of cases available for analysis.


Assuntos
Segunda Fase do Trabalho de Parto , Retenção Urinária , Gravidez , Feminino , Humanos , Estudos Retrospectivos , Retenção Urinária/epidemiologia , Retenção Urinária/etiologia , Parto Obstétrico/efeitos adversos , China
8.
J Minim Invasive Gynecol ; 30(9): 692, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37321296

RESUMO

OBJECTIVE: As a standard therapy for locally invasive cervical cancer, radical hysterectomy (RH) has been in routine medical practice for more than a century [1]. However, challenges still exist due to the troublesome bleeding during parametrium dissection and resection, which could increase the risk of surgical complications and may probably affect surgical outcomes ultimately [2]. This video illustrated the three-dimensional anatomy of the pelvic vascular system with particular emphasis on "deep uterine vein" and further introduced a vascular-centered surgical approach to performing RH, which could facilitate parametrium dissection with less blood loss and obtain enough resection margins. DESIGN: A step-by-step, narrated video demonstration SETTING: A university hospital INTERVENTIONS: After systemic pelvic lymphadenectomy, ureter was then identified along the medial leaf of the broad ligament. By continuously exploring the pelvic cavity along the ureter, communicating branches of the uterine artery to the ureter, urinary bladder, corpus uteri, uterine cervix, and upper vagina were clearly identified in a cranial to caudal direction, demonstrating the arterial network surrounding the urinary system. Coagulating and cutting these blood vessels could free the ureter from retroperitoneum and subsequently excavate the ureteral tunnel easily. Next, a precise dissection of the area below the ureter revealed the whole distribution of currently named "deep uterine vein". Originated from an internal iliac vein, it is much more like a venous confluence than an accompanying vein, with branches crossing directly into the bladder, dorsally to the rectum, and traveling caudally to the anterolateral side of the uterus and vagina in a crisscross fashion, which mandates us to describe it as pampiniform-like venous plexus instead of "deep uterine vein" due to its anatomical distribution and function. Finally, after complete exposure of venous network, enough extent of parametrium could be adequately separated and resected by accurate coagulation of blood vessels on an individualized requirement. CONCLUSION: Recognizing the precise anatomy of pelvic vascular system, especially the entire distribution of currently named "deep uterine vein" and isolating the venous branches connecting to all three parts of parametrium, are key to the RH procedure. Careful attention to the complex vascular anatomy is critical to reducing intraoperative bleeding and avoiding complications in RH.


Assuntos
Laparoscopia , Neoplasias do Colo do Útero , Feminino , Humanos , Histerectomia/métodos , Útero/irrigação sanguínea , Pelve/cirurgia , Neoplasias do Colo do Útero/cirurgia , Laparoscopia/métodos
9.
J Ovarian Res ; 16(1): 110, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37277766

RESUMO

BACKGROUND: The risk of suffering epithelial ovarian cancer (EOC) for women increases with age evidently, while the prognosis of older EOC patients remain unclear. Against the backdrop of the accelerate aging process in China, this paper investigates whether the older EOC patients have a lower overall survival probability than the younger patients based on the sample of ethnic Chinese population. METHODS: A total of 323 ethnic Chinese patients diagnosed as epithelial ovarian cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We compared the overall survival probability between the younger group (< 70 years) and the older patients group (≥ 70 years). Survival curves were drawn using the Kaplan-Meier method, comparisons among different subgroups were evaluated using log-rank tests, and independent prognostic factors were identified by univariate and multivariate Cox regression analyses. RESULTS: 43 patients were (13.3%) in the older patients group and 280 (86.7%) in the younger group. The distribution patterns between two groups were significantly different with regard to marital status, histologic type and FIGO stage. The median overall survival (OS) was significantly longer in the younger group than the older patients group (not reached vs. median 39 months, p < 0.05). The multivariate analysis demonstrated that the age (The older vs. the younger, HR: 1.967, P = 0.007), primary tumor laterality (HR: 1.849, P = 0.009), and FIGO stage (III vs. I, HR: 3.588, P = 0.001; and IV vs. I, HR: 4.382, P = 0.001; respectively) remained as important risk factors while Histology (HGSOC vs. CCOC, HR: 0.479, P = 0.025; and LGSOC/MOC/EC vs. CCOC, HR: 0.390, P = 0.034; respectively) and the number of lymph node dissected more than 10 was a protective factor (HR: 0.397, P = 0.008). In an analysis of 104 pairs of patients matched on the basis of the propensity score, the older patients group had significantly lower overall mortality (HR = 2.561, P = 0.002). CONCLUSION: Ethnic Chinese Older EOC patients have a worse prognosis than the younger patients.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Idoso , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/patologia , População do Leste Asiático , Prognóstico , Linfonodos/patologia
10.
Signal Transduct Target Ther ; 8(1): 183, 2023 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-37160887

RESUMO

Poly (ADP-ribose) polymerase (PARP) inhibitors are one of the most exciting classes of targeted therapy agents for cancers with homologous recombination (HR) deficiency. However, many patients without apparent HR defects also respond well to PARP inhibitors/cisplatin. The biomarker responsible for this mechanism remains unclear. Here, we identified a set of ribosomal genes that predict response to PARP inhibitors/cisplatin in HR-proficient patients. PARP inhibitor/cisplatin selectively eliminates cells with high expression of the eight genes in the identified panel via DNA damage (ATM) signaling-induced pro-apoptotic ribosomal stress, which along with ATM signaling-induced pro-survival HR repair constitutes a new model to balance the cell fate in response to DNA damage. Therefore, the combined examination of the gene panel along with HR status would allow for more precise predictions of clinical response to PARP inhibitor/cisplatin. The gene panel as an independent biomarker was validated by multiple published clinical datasets, as well as by an ovarian cancer organoids library we established. More importantly, its predictive value was further verified in a cohort of PARP inhibitor-treated ovarian cancer patients with both RNA-seq and WGS data. Furthermore, we identified several marketed drugs capable of upregulating the expression of the genes in the panel without causing HR deficiency in PARP inhibitor/cisplatin-resistant cell lines. These drugs enhance PARP inhibitor/cisplatin sensitivity in both intrinsically resistant organoids and cell lines with acquired resistance. Together, our study identifies a marker gene panel for HR-proficient patients and reveals a broader application of PARP inhibitor/cisplatin in cancer therapy.


Assuntos
Cisplatino , Neoplasias Ovarianas , Humanos , Feminino , Cisplatino/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Mutações Sintéticas Letais/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Ribossomos
11.
Clin Nucl Med ; 48(6): 525-527, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37133512

RESUMO

ABSTRACT: A 75-year-old woman presented with right lower abdominal pain. Pelvic ultrasound showed a cystic solid mass in the right adnexa. Painless enlarged lymph nodes on the left supraclavicular side with biopsy were suggestive of metastatic cancer. 18F-FDG PET/CT performed to evaluate the primary tumor showed intense uptake in both regions of the right adnexa and the gastric sinus, but 68Ga-FAPI PET/MRI showed uptake only in the right adnexal region. A subsequent gastroscopic biopsy confirmed atrophic inflammation. Finally, surgery histopathology revealed ovarian cancer. This case demonstrated that 68Ga-FAPI PET/MRI may help exclude suspected primary gastric carcinoma with false-positive 18F-FDG uptake.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Ovarianas , Feminino , Humanos , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Ovarianas/diagnóstico por imagem , Dor Abdominal
14.
Cancer Control ; 30: 10732748231159706, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36826231

RESUMO

Among the three primary gynecological malignancies, ovarian cancer has the lowest incidence but the worst prognosis. Because of the poor prognosis of ovarian cancer patients treated with existing treatments, immunotherapy is emerging as a potentially ideal alternative to surgery, chemotherapy, and targeted therapy. Among immunotherapies, immune checkpoint inhibitors have been the most thoroughly studied, and many drugs have been successfully used in the clinic. CD47, a novel immune checkpoint, provides insights into ovarian cancer immunotherapy. This review highlights the mechanisms of tumor immune evasion via CD47-mediated inhibition of phagocytosis and provides a comprehensive insight into the progress of the relevant targeted agents in ovarian cancer.


Assuntos
Antineoplásicos , Neoplasias , Neoplasias Ovarianas , Humanos , Feminino , Antígeno CD47/uso terapêutico , Fagocitose , Imunoterapia , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico
16.
Sci Rep ; 13(1): 2770, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36797331

RESUMO

To establish a deep learning (DL) model in differentiating borderline ovarian tumor (BOT) from epithelial ovarian cancer (EOC) on conventional MR imaging. We retrospectively enrolled 201 patients of 102 pathologically proven BOTs and 99 EOCs at OB/GYN hospital Fudan University, between January 2015 and December 2017. All imaging data were reviewed on picture archiving and communication systems (PACS) server. Both T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) MR images were used for lesion area determination. We trained a U-net++ model with deep supervision to segment the lesion area on MR images. Then, the segmented regions were fed into a classification model based on DL network to categorize ovarian masses automatically. For ovarian lesion segmentation, the mean dice similarity coefficient (DSC) of the trained U-net++ model in the testing dataset achieved 0.73 [Formula: see text] 0.25, 0.76 [Formula: see text] 0.18, and 0.60 [Formula: see text] 0.24 in the sagittal T2WI, coronal T2WI, and axial T1WI images, respectively. The DL model by combined T2WI computerized network could differentiate BOT from EOC with a significantly higher AUC of 0.87, an accuracy of 83.7%, a sensitivity of 75.0% and a specificity of 87.5%. In comparison, the AUC yielded by radiologist was only 0.75, with an accuracy of 75.5%, a sensitivity of 96.0% and specificity of 54.2% (P < 0.001).The trained DL network model derived from routine MR imaging could help to distinguish BOT from EOC with a high accuracy, which was superior to radiologists' assessment.


Assuntos
Aprendizado Profundo , Neoplasias Ovarianas , Feminino , Humanos , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Neoplasias Ovarianas/diagnóstico por imagem , Carcinoma Epitelial do Ovário
19.
Front Oncol ; 12: 975703, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212430

RESUMO

Background: Ovarian cancer (OC) is the most lethal gynecological malignancy, with limited early screening methods and poor prognosis. Artificial intelligence technology has made a great breakthrough in cancer diagnosis. Purpose: We aim to develop a specific interpretable machine learning (ML) prediction model for the diagnosis and prognosis of epithelial ovarian cancer (EOC) based on a variety of biomarkers. Methods: A total of 521 patients with EOC and 144 patients with benign gynecological diseases were enrolled including derivation datasets and an external validation cohort. The predicted information was acquired by 9 supervised ML methods, through 34 parameters. Behind predicted reasons for the best ML were improved by using the SHapley Additive exPlanations (SHAP) algorithm. In addition, the prognosis of EOC was analyzed by unsupervised clustering and Kaplan-Meier (KM) survival analysis. Results: ML technology was superior to conventional logistic regression in predicting EOC diagnosis and XGBoost performed best in the external validation datasets. The AUC values of distinguishing EOC and benign disease patients, determining pathological type, grade and clinical stage were 0.958 (0.926-0.989), 0.792 (0.701-0.8834), 0.819 (0.687-0.950) and 0.68 (0.573-0.788) respectively. For negative CA-125 EOC patients, the AUC performance of XGBoost model was 0.835(0.763-0.907). We used unsupervised cluster analysis to identify EOC subgroups with significantly poor overall survival (p-value <0.0001) and recurrence-free survival (p-value <0.0001). Conclusions: Based on the preoperative characteristics, we proved that ML algorithm can provide an acceptable diagnosis and prognosis prediction model for EOC patients. Meanwhile, SHAP analysis can improve the interpretability of ML models and contribute to precision medicine.

20.
Dis Markers ; 2022: 5940049, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36199822

RESUMO

The initiation and progression of cancer depend on the genetic alterations inherent in cancer cells, coupled with the mutual interplay of cancer cells with the surrounding tumor stroma. The platelet-derived growth factor (PDGF) family, as a mesenchymal growth factor, was involved in tumor progression by affecting the surrounding tumor stroma in some cancer types. However, the association of the PDGF family with the ovarian cancer stroma remains elusive. In our study, we first explored the expression pattern of the PDGF family using RNA expression profiles from public databases. We found that the PDGF family was highly expressed in tumor stroma compared with the corresponding epithelial components of ovarian cancer. In particular, PDGF receptors were weakly expressed in ovarian cancer tissues compared with the respective normal tissues; even in tumor mass, PDGF receptors were predominantly expressed by tumor stroma rather than ovarian cancer cells. Importantly, functional enrichment analyses and correlation analyses revealed that the PDGF family was strongly associated with activated stromal scores in ovarian cancer, including higher stromal scores, enriched pathways related to the extracellular matrix (ECM) organization and remodeling, elevated cancer-associated fibroblasts (CAFs) infiltration, and increased tumor-associated macrophages (TAMs) infiltration, especially macrophage M2. Besides, the positive correlations of the PDGF family with CAFs infiltration and macrophage M2 infiltration were observed in other various cancer types. Of note, the PDGF family was also involved in tumor progression-related pathways, such as transforming growth factor ß (TGF-ß) signaling, epithelial-mesenchymal transition (EMT), angiogenesis, and phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling. Higher expressions of PDGF receptors were also observed in ovarian cancer patients with venous or lymphatic invasion. Furthermore, we uncovered the prognostic prediction of the PDGF family in ovarian cancer and constructed a PDGF family-based risk prognosis model with a hazard ratio of 1.932 (95%confidence interval (CI) = 1.27-2.95) and P value < 0.01 (AUC = 0.782, 0.752 for 1 year and 2 years, respectively). Taken together, we demonstrated that ovarian cancers with high PDGF family expression biologically exhibit malignant progression behaviors as well as poor clinical survival, which is attributed to the activated tumor stroma in ovarian cancer.


Assuntos
Neoplasias Ovarianas , Fator de Crescimento Derivado de Plaquetas , Carcinoma Epitelial do Ovário , Feminino , Humanos , Neoplasias Ovarianas/patologia , Fosfatidilinositol 3-Quinases/genética , Fator de Crescimento Derivado de Plaquetas/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt , RNA , Receptores do Fator de Crescimento Derivado de Plaquetas , Fator de Crescimento Transformador beta/genética
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