scholarly journals In silico Approach for Validating and Unveiling New Applications for Prognostic Biomarkers of Endometrial Cancer

Cancers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 5052
Author(s):  
Eva Coll-de la Rubia ◽  
Elena Martinez-Garcia ◽  
Gunnar Dittmar ◽  
Petr V. Nazarov ◽  
Vicente Bebia ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Prognostic Factors ◽  
Histological Grade ◽  
Molecular Classification ◽  
Figo Stage ◽  
Prognostic Biomarkers ◽  
Free Survival ◽  
Prognostic Application ◽  
Potential Applications ◽  
New Applications

Endometrial cancer (EC) mortality is directly associated with the presence of prognostic factors. Current stratification systems are not accurate enough to predict the outcome of patients. Therefore, identifying more accurate prognostic EC biomarkers is crucial. We aimed to validate 255 prognostic biomarkers identified in multiple studies and explore their prognostic application by analyzing them in TCGA and CPTAC datasets. We analyzed the mRNA and proteomic expression data to assess the statistical prognostic performance of the 255 proteins. Significant biomarkers related to overall survival (OS) and recurrence-free survival (RFS) were combined and signatures generated. A total of 30 biomarkers were associated either to one or more of the following prognostic factors: histological type (n = 15), histological grade (n = 6), FIGO stage (n = 1), molecular classification (n = 16), or they were associated to OS (n = 11), and RFS (n = 5). A prognostic signature composed of 11 proteins increased the accuracy to predict OS (AUC = 0.827). The study validates and identifies new potential applications of 30 proteins as prognostic biomarkers and suggests to further study under-studied biomarkers such as TPX2, and confirms already used biomarkers such as MSH6, MSH2, or L1CAM. These results are expected to advance the quest for biomarkers to accurately assess the risk of EC patients.

Treatment outcomes of endometrial cancer patients with paraaortic lymph node metastasis: a multi-institutional analysis

2019 ◽  
Vol 29 (1) ◽  
pp. 94-101 ◽  
Author(s):  
Cem Onal ◽  
Berna Akkus Yildirim ◽  
Sezin Yuce Sari ◽  
Guler Yavas ◽  
Melis Gultekin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Prognostic Factors ◽  
Adjuvant Radiotherapy ◽  
Survival Rates ◽  
Myometrial Invasion ◽  
Progression Free Survival ◽  
Free Survival ◽  
Radiotherapy Alone ◽  
Paraaortic Lymph Node Metastasis

ObjectiveTo analyze the prognostic factors and treatment outcomes in endometrial cancer patients with paraaortic lymph node metastasis.MethodsData from four centers were collected retrospectively for 92 patients with endometrial cancer treated with combined radiotherapy and chemotherapy or adjuvant radiotherapy alone postoperatively, delivered by either the sandwich or sequential method. Prognostic factors affecting overall survival and progression-free survival were analyzed.ResultsThe 5-year overall survival and progression-free survival rates were 35 % and 33 %, respectively, after a median follow-up time of 33 months. The 5-year overall survival and progression-free survival rates were significantly higher in patients receiving radiotherapy and chemotherapy postoperatively compared with patients treated with adjuvant radiotherapy alone (P < 0.001 and P < 0.001, respectively). In a subgroup analysis of patients treated with adjuvant combined chemotherapy and radiotherapy, the 5-year overall survival and progression-free survival rates were significantly higher in patients receiving chemotherapy and radiotherapy via the sandwich method compared with patients treated with sequential chemotherapy and radiotherapy (P = 0.02 and P = 0.03, respectively). In the univariate analysis, in addition to treatment strategy, pathology, depth of myometrial invasion, and tumor grade were significant prognostic factors for both overall survival and progression-free survival. In the multivariate analysis, grade III disease, myometrial invasion greater than or equal to 50%, and adjuvant radiotherapy alone were negative predictors for both overall survival and progression-free survival.ConclusionWe demonstrated that adjuvant combined treatment including radiotherapyand chemotherapy significantly increases overall survival and progression-free survival rates compared with postoperative pelvic and paraaortic radiotherapy.

Prognostic Factors for Recurrence in Patients With FIGO Stage I and II Intermediate or High Risk Endometrial Cancer

2008 ◽  
Vol 63 (6) ◽  
pp. 369-370
Author(s):  
P L. M. Zusterzeel ◽  
R L. M. Bekkers ◽  
J C. M. Hendriks ◽  
D N. Neesham ◽  
R M. Rome ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Prognostic Factors ◽  
High Risk ◽  
Figo Stage ◽  
Stage I

scholarly journals Predictive Values of Programmed Cell Death-Ligand 1 Expression for Prognosis, Clinicopathological Factors, and Response to Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Inhibitors in Patients With Gynecological Cancers: A Meta-Analysis

2021 ◽  
Vol 10 ◽  
Author(s):  
Chen Zhang ◽  
Qing Yang
Keyword(s):  
Cell Death ◽  
Endometrial Cancer ◽  
Programmed Cell Death ◽  
Tumor Cells ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Figo Stage ◽  
Infiltration Depth ◽  
Gynecological Cancers ◽  
Free Survival

BackgroundThe prognostic value of programmed cell death-ligand 1 (PD-L1) in gynecological cancers has been explored previously, but the conclusion remains controversial due to limited evidence. This study aimed to conduct an updated meta-analysis to re-investigate the predictive significance of PD-L1 expression.MethodsPubMed, EMBASE and Cochrane Library databases were searched. The associations between PD-L1 expression status and prognosis [overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), cancer-specific survival (CSS) or disease-free survival (DFS)], clinical parameters [FIGO stage, lymph node metastasis (LNM), tumor size, infiltration depth, lymphovascular space invasion (LVSI) or grade] and response to anti-PD-1/PD-L1 treatment [objective response rate (ORR)] were analyzed by hazard ratios (HR) or relative risks (RR).ResultsFifty-five studies were enrolled. Overall, high PD-L1 expression was not significantly associated with OS, PFS, RFS, CSS and DFS of gynecological cancers. However, subgroup analysis of studies with reported HR (HR = 1.27) and a cut-off value of 5% (HR = 2.10) suggested that high PD-L1 expression was correlated with a shorter OS of gynecological cancer patients. Further sub-subgroup analysis revealed that high PD-L1 expressed on tumor-infiltrating immune cells (TICs) predicted a favorable OS for ovarian (HR = 0.72), but a poor OS for cervical cancer (HR = 3.44). PD-L1 overexpression was also correlated with a lower OS rate in non-Asian endometrial cancer (HR = 1.60). High level of PD-L1 was only clinically correlated with a shorter PFS in Asian endometrial cancer (HR = 1.59). Furthermore, PD-L1-positivity was correlated with LNM (for overall, ovarian and endometrial cancer expressed on tumor cells), advanced FIGO stage (for overall, ovarian cancer expressed on tumor cells, endometrial cancer expressed on tumor cells and TICs), LVSI (for overall and endometrial cancer expressed on tumor cells and TICs), and increasing infiltration depth/high grade (only for endometrial cancer expressed on TICs). Patients with PD-L1-positivity may obtain more benefit from anti-PD-1/PD-L1 treatment than the negative group, showing a higher ORR (RR = 1.98), longer OS (HR = 0.34) and PFS (HR = 0.61).ConclusionOur findings suggest high PD-L1 expression may be a suitable biomarker for predicting the clinical outcomes in patients with gynecological cancers.

Prognostic factors in FIGO stage IB cervical cancer without lymph node metastasis and the role of adjuvant radiotherapy after radical hysterectomy

2004 ◽  
Vol 14 (2) ◽  
pp. 286-292 ◽  
Author(s):  
A. Ayhan ◽  
R. A. Al ◽  
C. Baykal ◽  
E. Demirtas ◽  
A. Ayhan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Prognostic Factors ◽  
Lymph Node ◽  
Tumor Size ◽  
Adjuvant Radiotherapy ◽  
Disease Free Survival ◽  
Figo Stage ◽  
Free Survival ◽  
Stage Ib ◽  
Disease Free

Prognostic factors in FIGO stage IB cervical cancer without lymph node metastasis and the role of adjuvant radiotherapy after radical hysterectomy.ObjectivesThe aim of this study was to evaluate the clinical and pathologic prognostic variables for disease free survival, overall survival and the role of adjuvant radiotherapy in FIGO stage IB cervical carcinoma without lymph node metastasis.MethodsA retrospective review was performed of 393 patients with lymph node negative stage IB cervical cancer treated by type 3 hysterectomy and pelvic lymphadenectomy at the Hacettepe University Hospitals between 1980 and 1997.ResultsThe disease free survival and overall survival were 87.6 and 91.0%, respectively. In univariate analysis, tumor size, depth of invasion, vaginal involvement, lympho-vascular space involvement (LVSI) and adjuvant radiotherapy were found significant in disease free survival. Overall survival was affected by tumor size, LVSI, vaginal involvement and adjuvant radiotherapy. Tumor size, LVSI and vaginal involvement were found as independent prognostic factors for overall and disease free survival in multivariate analysis. Disease free survival, recurrence rate and site did not differ between patients underwent radical surgery and radical surgery plus radiotherapy.ConclusionTumor size, LVSI and vaginal involvement were independent prognostic factors in lymph node negative FIGO stage IB cervical cancer. Adjuvant radiotherapy in stage IB cervical cancer patients with negative nodes provides no survival advantage or better local tumoral control.

scholarly journals FIGO 2018 stage IB endocervical adenocarcinomas: an international study of outcomes informed by prognostic biomarkers

2020 ◽  
pp. ijgc-2020-001893
Author(s):  
Simona Stolnicu ◽  
Monica Boros ◽  
Lien Hoang ◽  
Noorah Almadani ◽  
Louise de Brot ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lymph Node ◽  
Lymphovascular Invasion ◽  
Figo Stage ◽  
Prognostic Biomarkers ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Stage Ib ◽  
Gynecology And Obstetrics ◽  
Hpv Status

ObjectivePrognostic factors for endocervical adernocarcinomas are well known, but little is known about prognostic biomarkers influencing outcome for the newly defined International Federation of Gynecology and Obstetrics (FIGO) 2018 IB sub-stages. The aim of this study was to identify prognostic biomarkers influencing recurrence-free and overall survival for FIGO 2018 stage IB cervical adenocarcinoma sub-types. We sought to identify these factors using a large international multi-institutional series of cases.MethodsStage IB endocervical adenocarcinomas were retrospectively collected from nine international institutions; full slide sets (n=464) were used to assign prognostic biomarkers. Inclusion criteria were the following: FIGO stage IB endocervical adenocarcinomas with follow-up in which all paraffin blocks/glass slides were available for review and/or additional studies and the patient was surgically treated from 1985 to 2019. The types of specimens included in the study were conizations, trachelectomies, and simple/radical hysterectomies with or without lymph node samples. We excluded in situ carcinomas, squamous cell carcinomas, adenosquamous carcinomas, tumors with a neuroendocrine component, carcinosarcomas, and any tumor showing clinical, macroscopic, or microscopic features suggesting a lower uterine segment, uterine corpus, or an adnexal primary origin. Tumors treated with neoadjuvant chemotherapy and/or radiation therapy were also excluded, as well as biopsies and loop electrosurgical excision procedures.ResultsOf 464 cases, 225 (48%) were stage IB1, 177 (38%) were stage IB2, and 62 (13%) were stage IB3. Five-year and 10-year recurrence-free survivals were statistically different among stage IB sub-types (p=0.005). Silva pattern of invasion was significant for recurrence-free survival at 5 and 10 years (p=0.04); overall survival and recurrence-free survival were higher in human papillomavirus (HPV)-associated cases (p=0.007 and p=0.001, respectively) and in cases without lymphovascular invasion (p=0.004 and p=0.00001, respectively). Factors that significantly influenced recurrence-free survival were HPV-independent status (p=0.05; HR 2.31; 95% CI 1.02 to 5.46), presence of lymphovascular invasion (p=0.011; HR 3.50; 95% CI 1.33 to 9.19), and presence of lymph node metastasis (p=0.016; HR 2.66; 95% CI 1.20 to 5.90).ConclusionHPV status and the presence of lymphovascular invasion are prognosticators in stage IB endocervical adenocarcinoma sub-types. These parameters should be included in future sub-staging modifications of FIGO stage IB endocervical adenocarcinomas and in treatment strategies.

scholarly journals Prognostic Biomarkers in Endometrial Cancer: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 9 (6) ◽  
pp. 1900 ◽  
Author(s):  
Eva Coll-de la Rubia ◽  
Elena Martinez-Garcia ◽  
Gunnar Dittmar ◽  
Antonio Gil-Moreno ◽  
Silvia Cabrera ◽  
...  
Keyword(s):  
Systematic Review ◽  
Endometrial Cancer ◽  
Prognostic Factors ◽  
Tumor Recurrence ◽  
Meta Analysis ◽  
Prognostic Biomarkers ◽  
Protein Biomarkers ◽  
Common Cancer ◽  
Pubmed Database ◽  
Mmr Proteins

Endometrial cancer (EC) is the sixth most common cancer in women worldwide and its mortality is directly associated with the presence of poor prognostic factors driving tumor recurrence. Stratification systems are based on few molecular, and mostly clinical and pathological parameters, but these systems remain inaccurate. Therefore, identifying prognostic EC biomarkers is crucial for improving risk assessment pre- and postoperatively and to guide treatment decisions. This systematic review gathers all protein biomarkers associated with clinical prognostic factors of EC, recurrence and survival. Relevant studies were identified by searching the PubMed database from 1991 to February 2020. A total number of 398 studies matched our criteria, which compiled 255 proteins associated with the prognosis of EC. MUC16, ESR1, PGR, TP53, WFDC2, MKI67, ERBB2, L1CAM, CDH1, PTEN and MMR proteins are the most validated biomarkers. On the basis of our meta-analysis ESR1, TP53 and WFDC2 showed potential usefulness for predicting overall survival in EC. Limitations of the published studies in terms of appropriate study design, lack of high-throughput measurements, and statistical deficiencies are highlighted, and new approaches and perspectives for the identification and validation of clinically valuable EC prognostic biomarkers are discussed.

Survival and prognostic factors in patients with epithelial ovarian cancer receiving paclitaxel and carboplatin as first-line chemotherapy in Japanese women: A multi-center retrospective study

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15022-15022
Author(s):  
H. Kajiyama ◽  
F. Kikkawa ◽  
M. Kawai ◽  
K. Mizuno ◽  
I. Kobayashi ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Prognostic Factors ◽  
Retrospective Study ◽  
Epithelial Ovarian Cancer ◽  
Clear Cell ◽  
Histological Grade ◽  
Clinical Stage ◽  
Progression Free Survival ◽  
Figo Stage ◽  
Second Line

15022 Background: The aim of this retrospective study was to re-evaluate, multi-analytically, survival and prognostic factors of patients with epithelial ovarian cancer (EOC) receiving the combination of paclitaxel and carboplatin (PC). Methods: Between 1/00 and 12/04, a total of 335 cases with EOC of FIGO stage I-IV are registered in a multi-institutional series. All patients received cytoreductive surgery and combination chemotherapy of paclitaxel 180 mg/m2/3 hr and carboplatiion AUC = 5 for a total of 6 cycles. We retrospectively analyzed progression-free survival (PFS) and overall survival (OS) of these patients by stratification of assumable several prognostic factors and second-line regimen. Survival probabilities were estimated by Kaplan-Meier methods, and prognostic factors for survival were evaluated by a COX proportional hazard model. Results: Median age was 54 ± 11 years (range 9–81). The 3-, 4- and 5-year OS in patients was 67.0%, 53.9% and 50.6%, respectively. In a COX analysis, FIGO stage, histological type and residual tumor (2 cm < vs. 2 cm >; P = 0.0007, HR; 2.4, 95% CI = 1.4–4.0) were found to be independent significant factors for OS. The stratification analysis revealed that stage III-IV patients with clear cell and mucinous carcinoma have poorer prognosis than those with other histological types ( Table ). In contrast, no differences in histological grade (G1 vs. G2; P = 0.82, HR; 0.9, 95% CI = 0.5–1.6, G1 vs. G3; P = 0.65, HR; 0.9, 95% CI = 0.4–1.6) and kinds of second-line regimen were noticed for PFS and OS. Conclusions: Optimal surgical debulking, clinical stage, and histology appear to be important prognostic factors of survival in patients with EOC. This retrospective study suggests that PC may still have an impact on outcome. However, further strategy will be needed for improving survival of mucinous and clear-cell type EOC, especially with advanced stage. [Table: see text] No significant financial relationships to disclose.

Tumor-associated CD66b+ neutrophil and CD8+ lymphocyte densities as independent prognostic factors for recurrence in localized cervical cancer: Automated digital image analysis and observer-assisted stereological assessments.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5532-5532
Author(s):  
Andreas Carus ◽  
Morten Ladekarl ◽  
Patricia Switten Nielsen ◽  
Henrik Hager ◽  
Bettina S Nedergaard ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Image Analysis ◽  
Prognostic Factors ◽  
Digital Image ◽  
Digital Image Analysis ◽  
Figo Stage ◽  
Prognostic Impact ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Macrophage Density

5532 Background: The prognostic impact of tumor-associated immune cells in cervical cancer is unclear. Methods: Automated digital image analysis (DIA) software and observer-assisted stereological (OAS) assessments were used to obtain densities of immunostains for CD66b+ neutrophils, CD163+ macrophages, and CD8+lymphocytes in scanned whole slide images of tumor sections from 101 patients with FIGO stage IB and IIA cervical cancer. Primary end-point was recurrence-free survival (RFS). Results: The highest densities of CD66b+ neutrophils and CD163+ macrophages were observed by OAS in the peritumoral compartment (median 53.1 cells/mm2 and 1.3% area fraction, respectively). DIA required far less human resources than OAS assessments. We observed high correlations between DIA and OAS variables of corresponding parameters; spearman ρ was 0.79 for CD8+ lymphocytes , 0.85 for CD66b+ neutrophils, and 0.92 for CD163+ macrophages (all p <0.0001). Hazard rates for DIA assessments in the global tumor area were comparable with the prognostically strongest OAS assessments in the peritumoral compartment. In multivariate analysis, high density of CD66b+ neutrophils (HR 2.6; 95% CI 1.2–5.7; p = 0.02), low density of CD8+ lymphocytes (HR 2.3; 95% CI 1.1–4.9; p = 0.03), and presence of lymph node metastases (HR 2.6; 95% CI 1.2–5.5; p = 0.02) were independent predictors of poor RFS, whereas FIGO stage and CD163+macrophage density were not. The CD66b/CD8 immunostain index obtained by DIA had excellent discriminatory power for each quartile with 5-year RFS of 92%, 80%, 65%, and 48% for quartile I (<0.019), II (0.02-0.05), III (0.06-0.24), and IV (>0.25), respectively (p = 0.001). Conclusions: High tumor-associated CD66b+ neutrophil and low CD8+ lymphocyte densities are independent prognostic factors for short recurrence-free survival in cervical cancer assessed by DIA and OAS. Combined CD66b+ neutrophil/CD8+ lymphocyte immunostain index obtained by DIA is a strong and cost-efficient prognostic variable with potential for routine application.

Prognostic factors for recurrence in patients with FIGO stage I and II, intermediate or high risk endometrial cancer

2008 ◽  
Vol 87 (2) ◽  
pp. 240-246 ◽  
Author(s):  
P.L.M. Zusterzeel ◽  
R.L.M. Bekkers ◽  
J.C.M. Hendriks ◽  
D.N. Neesham ◽  
R.M. Rome ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Prognostic Factors ◽  
High Risk ◽  
Figo Stage ◽  
Stage I

scholarly journals The effect of myometrial invasion on prognostic factors and survival analysis in endometrial carcinoma

1970 ◽  
Vol 19 (4) ◽  
pp. 3235-3241
Author(s):  
Cem Dane ◽  
Sait Bakir
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Prognostic Factors ◽  
Survival Rate ◽  
Endometrial Carcinoma ◽  
Myometrial Invasion ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Free Survival ◽  
The Relationship

Background: We investigated the relationship between myometrial invasion and the prognostic factors on overall and progression free survival in endometrial carcinoma.Methods: 122 cases operated with endometrial cancer were included into the study. Progression-free survival and overall survival were evaluated according to degree of myometrial invasion. We also investigated the relationship between myometrial invasion and prognostic factors. Results: The 5- year progression-free survival rate was 90 % in stage I, 66 % in stage II, 32 % in stage III and 60 % in stage IV. The 5- year overall survival rate was 95 % in stage I, 89 % in stage II, 49 % in stage III and 30 % in stage IV. The progression free survival and overall survival for patients with more than 50 % myometrial invasion were detected 67 % at 58 months and 66 % at 60 months, respectively. The clinicopathological variables that significantly correlated with myometrial invasion of more than 50 % were as follows: pelvic lymph node metastasis (p: 0,00029-OR: 11.2), cervical stromal invasion (p: 0008-OR:7.9), LVSI (p< 0.0001-OR: 16.5).Conclusion: The depth of myometrial invasion is one of the most important prognostic indicators and determinants of therapy in endometrial cancer. Keywords: Endometrial carcinoma; Progression free survival; Overall survival; Prognostic factors.

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