Construction and Validation of a Prognostic Model Based on 11 Lymph Node Metastasis Related Genes for Overall Survival in Endometrial Cancer

2021 ◽  
Author(s):  
Hong Wu ◽  
haiqin Feng ◽  
Xiaoli Miao ◽  
jiancai Ma ◽  
Cairu Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Prognostic Model ◽  
Risk Model ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Low Risk ◽  
Node Metastasis

Abstract Background: Endometrial cancer (EC) is one of the most common malignant tumor in the female reproductive system. The incidence of lymph node metastasis (LNM) is only about 10% in clinically suspected early-stage EC patients. Discovering prognostic model and effective biomarkers for early diagnosis is important to reduce the mortality rate. Methods: We downloaded the RNA-sequencing data and clinical information from the TCGA database. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the differentially expressed genes (DEGs). A least absolute shrinkage and selection operator (LASSO) regression was conducted to identify the characteristic dimension decrease and distinguish prognosis-related LNM related genes signature. Subsequently, a novel prognosis-related nomogram to predict overall survival (OS). A survival analysis was carried out to explore the individual prognostic significance of the risk model and key gene was validated in vitro. Results: In total, 89 LRGs were identified. Based on the LASSO Cox regression, 11 genes were selected for the development of a risk evaluation model. The Kaplan–Meier curve indicated that patients in the low-risk group had considerably better OS (P = 3.583e−08). The area under the curve (AUC) of this model was 0.718 at 5 years of OS. Then, we developed an OS-associated nomogram that included the risk score and clinicopathological features. The concordance index of the nomogram was 0.769. The survival verification performed in three subgroups from the nomogram demonstrated the validity of the model. The AUC of the nomogram was 0.787 at 5 years OS. Proliferation and metastasis of HMGB3 were explored in EC cell line. Finally, we revealed that the most frequently mutated genes in the low-risk and high-risk groups are PTEN and TP53, respectively. Conclusions: Our results suggest that LNM plays an important role in the prognosis, and HMGB3 was potential as a biomarker for EC patients. By detecting the mutation of the risk signature, clinicians can accurately treat patients with targeted therapy, thereby improving their survival rate.

scholarly journals Cervical invasion, lymphovascular space invasion, and ovarian metastasis as predictors of lymph node metastasis and poor outcome on stages I to III endometrial cancers: a single-center retrospective study

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Min Li ◽  
Shuwei Wu ◽  
Yangqin Xie ◽  
Xiaohui Zhang ◽  
Zhanyu Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Regression Models ◽  
Cox Regression ◽  
Myometrial Invasion ◽  
Ovarian Metastasis ◽  
Surgical Staging ◽  
Tumor Diameter ◽  
Node Metastasis

Abstract Background The aim of this study is to determine pathological factors that increase the risk of LNM and indicate poor survival of patients diagnosed with endometrial cancer and treated with surgical staging. Method Between January 2010 and November 2018, we enrolled 874 eligible patients who received staging surgery in the First Affiliated Hospital of Anhui Medical University. The roles of prognostic risk factors, such as age, histological subtype, tumor grade, myometrial infiltration, tumor diameter, cervical infiltration, lymphopoiesis space invasion (LVSI), CA125, and ascites, were evaluated. Multivariable logistic regression models were used to identify the predictors of LNM. Kaplan–Meier and COX regression models were utilized to study the overall survival. Results Multivariable regression analysis confirmed cervical stromal invasion (OR 3.412, 95% CI 1.631–7.141; P < 0.01), LVSI (OR 2.542, 95% CI 1.061–6.004; P = 0.04) and ovarian metastasis (OR 6.236, 95% CI 1.561–24.904; P = 0.01) as significant predictors of nodal dissemination. Furthermore, pathological pattern (P = 0.03), myometrial invasion (OR 2.70, 95% CI 1.139–6.40; P = 0.01), and lymph node metastasis (OR 9.675, 95% CI 3.708–25.245; P < 0.01) were independent predictors of decreased overall survival. Conclusions Cervical invasion, lymphopoiesis space invasion, and ovarian metastasis significantly convey the risk of LNM. Pathological type, myometrial invasion, and lymph node metastasis are all important predictors of survival and should be scheduled for completion when possible in the surgical staging procedure.

Detection of Lymphovascular Invasion by D2-40 (Podoplanin) Immunoexpression in Endometrial Cancer

2012 ◽  
Vol 22 (8) ◽  
pp. 1442-1448 ◽  
Author(s):  
Sarah K. Weber ◽  
Axel Sauerwald ◽  
Martin Pölcher ◽  
Michael Braun ◽  
Manuel Debald ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Lymphovascular Invasion ◽  
Lymph Node Involvement ◽  
Lymph Vessel ◽  
Node Metastasis ◽  
Lymph Vessel Invasion ◽  
Node Involvement

BackgroundLymph node involvement is a major feature in tumor spread of endometrial cancer and predicts prognosis. Therefore, evaluation of lymph vessel invasion (LVI) in tumor tissue as a predictor for lymph node metastasis is of great importance. Immunostaining of D2-40 (podoplanin), a specific marker for lymphatic endothelial cells, might be able to increase the detection rate of LVI compared with conventional hematoxylin-eosin (H-E) staining. The aim of this retrospective study was to analyze the eligibility of D2-40–based LVI evaluation for the prediction of lymph node metastases and patients’ outcome.Patients and MethodsImmunohistochemical staining with D2-40 monoclonal antibodies was performed on paraffin-embedded tissue sections of 182 patients with primary endometrioid adenocarcinoma treated in 1 gynecologic cancer center. Tumors were screened for the presence of LVI. Correlations with clinicopathological features and clinical outcome were assessed.ResultsImmunostaining of D2-40 significantly increased the frequency LVI detection compared with conventional H-E staining. Lymph vessel invasion was identified by D2-40 in 53 (29.1%) of 182 tumors compared with 34 (18.3%) of 182 carcinomas by routine H-E staining (P = 0.001). D2-40 LVI was detectable in 81.0% (17/21) of nodal-positive tumors and significantly predicted lymph node metastasis (P = 0.001). Furthermore, D2-40 LVI was an independent prognostic factor for patients overall survival considering tumor stage, lymph node involvement, and tumor differentiation (P < 0.01). D2-40–negative tumors confined to the inner half of the myometrium showed an excellent outcome (5-year overall survival, 97.8%).ConclusionsD2-40–based LVI assessment improves the histopathological detection of lymphovascular invasion in endometrial cancer. Furthermore, LVI is of prognostic value and predicts lymph node metastasis. D2-40 LVI detection might help to select endometrial cancer patients who will benefit from a lymphadenectomy.

scholarly journals Implications of Isolated Para-Aortic Lymph Node Metastasis in Endometrial Cancer: A Large-Scale, Multicenter, and Retrospective Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Wenting Li ◽  
Jie Jiang ◽  
Yu Fu ◽  
Yuanming Shen ◽  
Chuyao Zhang ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Large Scale ◽  
Low Risk ◽  
Surgical Staging ◽  
Node Metastasis ◽  
Aortic Lymph Node ◽  
Risk Patients ◽  
Metastatic Sites

Objective: To systematically evaluate lymph node metastasis (LNM) patterns in patients with endometrial cancer (EC) who underwent complete surgical staging, which included systematic pelvic and para-aortic lymphadenectomy.Methods: Four thousand and one patients who underwent complete surgical staging including systematic pelvic and para-aortic lymphadenectomy for EC were enrolled from 30 centers in China from 2001 to 2019. We systematically displayed the clinical and prognostic characteristics of patients with various LNM patterns, especially the PLN-PAN+ [para-aortic lymph node (PAN) metastasis without pelvic lymph node (PLN) metastasis]. The efficacy of PAN+ (para-aortic lymph node metastasis) prediction with clinical and pathological features was evaluated.Results: Overall, 431 of the 4,001 patients (10.8%) showed definite LNM according to pathological diagnosis. The PAN+ showed the highest frequency (6.6%) among all metastatic sites. One hundred fourteen cases (26.5%) were PLN-PAN+ (PAN metastasis without PLN metastasis), 167 cases (38.7%) showed PLN+PAN-(PLN metastasis without PAN metastasis), and 150 cases (34.8%) showed metastasis to both regions (PLN+PAN+). There was also 1.9% (51/2,660) of low-risk patients who had PLN-PAN+. There are no statistical differences in relapse-free survival (RFS) and disease-specific survival (DSS) among PLN+PAN-, PLN-PAN+, and PLN+PAN+. The sensitivity of gross PLNs, gross PANs, and lymphovascular space involvement (LVSI) to predict PAN+ was 53.8 [95% confidence interval (CI): 47.6–59.9], 74.2 95% CI: 65.6–81.4), and 45.8% (95% CI: 38.7–53.2), respectively.Conclusion: Over one-fourth of EC patients with LMN metastases were PLN-PAN+. PLN-PAN+ shares approximate survival outcomes (RFS and DSS) with other LNM patterns. No effective clinical methods were achieved for predicting PAN+. Thus, PLN-PAN+ is a non-negligible LNM pattern that cannot be underestimated in EC, even in low-risk patients.

scholarly journals Construction of a novel ferroptosis-related gene signature for predicting prognosis and immune microenvironment in acute myeloid leukemia

2021 ◽  
Author(s):  
Xianbo Huang ◽  
De Zhou ◽  
Xiujin Ye ◽  
Jie Jin
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Risk Model ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Risk Groups ◽  
Low Risk ◽  
Cox Regression Analysis ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a highly heterogeneous hematopoietic malignancy that strongly correlates with poor clinical outcomes. Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death which plays an important role in various human cancers. Nevertheless, the prognostic significance and functions of ferroptosis-related genes (FRGs) in AML have not received sufficient attention. The aim of this article was to evaluate the association between FRGs levels and AML prognosis using publicly available RNA-sequencing datasets. The univariate Cox regression analysis identified 20 FRGs that correlate with patient overall survival. The LASSO Cox regression model was used to construct a prognostic 12-gene risk model using a TCGA cohort, and internal and external validation proved the signature efficient. The 12-FRGs signature was then used to assign patients into high- and low-risk groups, with the former exhibiting markedly reduced overall survival, compared to the low-risk group. ROC curve analysis verified the predictive ability of the risk model. Functional analysis showed that immune status and drug sensitivity differed between the 2 risk groups. In summary, FRGs is a promising candidate biomarker and therapeutic target for AML.

scholarly journals PD-L1 Expression Is an Independent Marker for Lymph Node Metastasis in Middle Eastern Endometrial Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 394
Author(s):  
Abdul K. Siraj ◽  
Sandeep Kumar Parvathareddy ◽  
Padmanaban Annaiyappanaidu ◽  
Nabil Siraj ◽  
Maha Al-Rasheed ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Tumor Cells ◽  
Middle Eastern ◽  
Prognostic Significance ◽  
Independent Prognostic Marker ◽  
Node Metastasis ◽  
Protein Status ◽  
Impact On Survival

Programmed death ligand 1 (PD-L1) expression in endometrial cancer (EC) tumor cells have been reported in several studies with inconsistent results. Furthermore, there is scarcity of data on the prevalence and prognostic significance of PD-L1 expression in EC from Middle Eastern ethnicity. We aimed to assess PD-L1 expression in a large cohort of Middle Eastern EC and to correlate this with clinico-pathological factors, as well as mismatch repair (MMR) protein status and patients’ outcome. PD-L1 expression was investigated using immunohistochemistry on tissue microarray in an unselected cohort of 440 EC. Kaplan–Meier and logistic regression analysis were used to compare the outcome and prognostic factors. PD-L1 expression in tumor tissue was detected in 18.9% (83/440) EC cases with no impact on survival. When stratified for MMR protein status, PD-L1 expression was similar for both MMR deficient and MMR proficient ECs. However, the expression of PD-L1 in tumor cells was significantly associated with type II (non-endometrioid) histology (p = 0.0005) and lymph node metastasis (p = 0.0172). Multivariate analysis showed PD-L1 expression to be an independent risk factor for lymph node metastasis (odds ratio: 2.94; 95% CI: 1.26–6.84; p = 0.0123). In conclusion, PD-L1 was strongly associated with non-endometrioid EC and was an independent prognostic marker of lymph node metastasis.

Preoperative Identification of a Low-Risk Group for Lymph Node Metastasis in Endometrial Cancer: A Korean Gynecologic Oncology Group Study

2012 ◽  
Vol 30 (12) ◽  
pp. 1329-1334 ◽  
Author(s):  
Sokbom Kang ◽  
Woo Dae Kang ◽  
Hyun Hoon Chung ◽  
Dae Hoon Jeong ◽  
Sang-Soo Seo ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Risk Group ◽  
False Negative ◽  
False Negative Rate ◽  
Low Risk ◽  
Ca 125 ◽  
Node Metastasis ◽  
Negative Rate

Purpose The aim of this study was to develop a preoperative risk prediction model for lymph node metastasis in patients with endometrial cancer and to identify a low-risk group before surgery. Patients and Methods The medical records of 360 patients with endometrial cancer who underwent surgical staging were collected from four institutions and were retrospectively reviewed. By using serum CA-125 levels, preoperative biopsy data, and magnetic resonance imaging (MRI) data, a multivariate logistic model was created. Patients whose predicted probability was less than 4% were defined as low risk. The developed model was externally validated in 180 patients from two independent institutions. Results Serum CA-125 levels and three MRI parameters (deep myometrial invasion, lymph node enlargement, and extension beyond uterine corpus) were found to be independent risk factors for nodal metastasis. The model classified 53% of patients as part of a low-risk group, and the false negative rate was 1.7%. In the validation cohort, the model classified 43% of patients as low-risk, and the false negative rate was 1.4%. The model showed good discrimination (area under the receiver operator characteristic curve = 0.85) and was calibrated well. The negative likelihood ratio of our low-risk criteria was 0.11 (95% CI, 0.04 to 0.29), which was equivalent to the false-negative rate of 1.3% (95% CI, 0.5% to 3.3%) at the assumed prevalence of nodal metastasis of 10%. Conclusion Using serum CA-125 and MRI as criteria resulted in the accurate identification of a low-risk group for lymph node metastasis among patients with endometrial cancer.

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