scholarly journals A Prognostic Gene Signature Expressed in Primary Cutaneous Melanoma: Synergism With Conventional Staging

2018 ◽  
Vol 2 (3) ◽  
Author(s):  
Georg Brunner ◽  
Achim Heinecke ◽  
Thomas M Falk ◽  
Beyhan Ertas ◽  
Norbert Blödorn-Schlicht ◽  
...  
Keyword(s):  
Cutaneous Melanoma ◽  
Statistical Tests ◽  
Characteristic Curve ◽  
Multivariable Analysis ◽  
Area Under The Curve ◽  
Gene Signature ◽  
Primary Cutaneous Melanoma ◽  
Specific Patient ◽  
Ajcc Staging ◽  
Conventional Staging

Abstract Background Current clinico-pathological American Joint Committee on Cancer (AJCC) staging of primary cutaneous melanoma is limited in its ability to determine clinical outcome, and complementary biomarkers are not available for routine prognostic assessment. We therefore adapted a gene signature, previously identified in fresh-frozen (FF) melanomas and adjacent stroma, to formalin-fixed paraffin-embedded (FFPE) melanomas. The aim was to develop a gene expression profiling (GEP) score to define patient survival probability at the time of first diagnosis. Methods Expression of 11 FF melanoma signature genes was quantified by reverse transcription polymerase chain reaction in an FFPE melanoma training cohort (n = 125), corresponding to the combined FF melanoma training and validation cohorts. The resulting GEP score was validated technically and clinically in an independent FFPE melanoma cohort (n = 211). All statistical tests were two-sided. Results We identified a prognostic eight-gene signature in the tumor area (tumor and adjacent tissue) of AJCC stage I–III melanomas. A signature-based GEP score correlated with melanoma-specific survival (MSS; Kaplan-Meier analysis: P < .0001) was independent of tumor stage (multivariable regression analysis: P = .0032) and stroma content (<5%–90%) and complemented conventional AJCC staging (receiver operating characteristic curve analysis: area under the curve = 0.91). In the clinical validation cohort, the GEP score remained statistically significant (P = .0131) in a multivariable analysis accounting for conventional staging. The GEP score was technically robust (reproducibility: 93%; n = 84) and clinically useful, as a binary as well as a continuous score, in predicting stage-specific patient MSS. Conclusions The GEP score is a clinically significant prognostic tool, contributes additional information regarding the MSS of melanoma patients, and complements conventional staging.

scholarly journals Changes in perfusion can detect changes in the cardiac index in patients with septic shock

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052093167
Author(s):  
Hui Lian ◽  
Xiaoting Wang ◽  
Qing Zhang ◽  
Hongmin Zhang ◽  
Dawei Liu
Keyword(s):  
Septic Shock ◽  
Cardiac Index ◽  
Characteristic Curve ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Area Under The Curve ◽  
Treatment Phase ◽  
Cardiac Output Monitoring ◽  
Fluid Loading ◽  
Output Monitoring

Objective The perfusion index (PI) is usually used to assess peripheral perfusion, which can be influenced by the cardiac index (CI). CI monitoring is often needed during the treatment of patients with shock. We investigated the relationship between changes in the PI (ΔPI) and changes in the CI (ΔCI) in patients with septic shock. Methods This retrospective study included patients with septic shock who underwent pulse-induced continuous cardiac output monitoring. We measured the CI and PI before and after fluid loading during the first 6 hours of intensive care unit admission. Fluid responsiveness was defined as a ≥10% ΔCI after fluid loading. Other hemodynamic and oxygen-derived parameters were also collected at the exact time of each CI measurement. Results Fifty-five patients were included in the study (29 fluid responders, 26 fluid non-responders). In the univariate analysis, ΔPI was positively correlated with ΔCI. In the multivariable analysis, ΔPI was independently associated with ΔCI. The receiver operating characteristic curve showed that ΔPI was an appropriate marker with which to discriminate a CI increase with an area under the curve of 0.776. Conclusion This study showed a positive correlation between ΔPI and ΔCI during the early treatment phase of septic shock.

Validation, in silico and in vitro, of a gene-signature based risk score in cutaneous melanoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9560-9560 ◽  
Author(s):  
Georg Brunner ◽  
Thomas M. Falk ◽  
Beyhan Ertas ◽  
Carola Berking ◽  
Hans-Joachim Schulze ◽  
...  
Keyword(s):  
Risk Score ◽  
Cutaneous Melanoma ◽  
In Silico ◽  
Patient Survival ◽  
Gene Signature ◽  
Hazard Ratio ◽  
Training Cohort ◽  
Signature Genes ◽  
Ajcc Staging

9560 Background: Melanoma staging, as defined by the American Joint Committee on Cancer (AJCC), is limited in its ability to predict outcome. We have previously identified and validated a prognostic gene signature expressed in primary cutaneous melanoma and adjacent stroma. The signature comprises seven protective genes (down-regulated with tumor progression) and one risk-associated gene (up-regulated). A signature-based risk score independently predicts patient survival, across AJCC stages IA-IIIC, in formalin-fixed, paraffin-embedded (FFPE) melanomas (training cohort, n = 125; p = 0.0003, hazard ratio 1.85). The score has been validated in 206 melanomas, selected to be significantly mis-prognosticated by AJCC staging regarding patient survival (40.8% mis-prognostication). In this cohort, the score outperforms AJCC staging (p = 0.0005, hazard ratio 1.41 vs. p = n.s.), correcting 34.9% of AJCC-based mis-prognostications. Methods: Here, we report twofold external validation of the risk score, (i) prognostic performance in silico using the SurvExpress web tool (Aguirre-Gamboa et al., 2013), and (ii) technical performance in vitro(Dermatologikum Hamburg; IMGM Munich) . Results: (i) Kaplan Meier analysis and log-rank testing demonstrated that all signature genes combined predicted survival in four different cohorts of metastatic melanoma (from GEO Expression Omnibus or Cancer Genome Atlas; cohorts dichotomized at the median): see table. (ii) The risk score was re-analyzed in melanomas of the training cohort (n=69). The overall concordance of duplicate determinations was 90% (average scores of 1.12 ± 0.14 and 0.97 ± 0.14). Conclusions: In conclusion, we have validated a signature-based FFPE melanoma risk score, complementary to AJCC staging in predicting outcome: (i) Signature genes predicted patient survival in silico(n=449) (ii) The risk score proved to be reproducible and technically robust in vitro. The score improves risk stratification and decision making in melanoma, particularly regarding new adjuvant therapies. [Table: see text]

Reproducibility of AJCC Staging Parameters in Primary Cutaneous Melanoma: An Analysis of 4,924 Cases

2013 ◽  
Vol 20 (12) ◽  
pp. 3969-3975 ◽  
Author(s):  
Maarten G. Niebling ◽  
Lauren E. Haydu ◽  
Rooshdiya Z. Karim ◽  
John F. Thompson ◽  
Richard A. Scolyer
Keyword(s):  
Cutaneous Melanoma ◽  
Primary Cutaneous Melanoma ◽  
Ajcc Staging

scholarly journals A Novel Prognostic Biomarker of Luminal Breast Cancer: High CD39 Expression Is Related to Poor Survival

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaojian Ni ◽  
Wenze Wan ◽  
Jingjing Ma ◽  
Xinyou Liu ◽  
Bohao Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cell ◽  
Statistical Tests ◽  
Characteristic Curve ◽  
Multivariable Analysis ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Luminal Breast Cancer ◽  
Functional Surface

BackgroundCD39 is one of the functional surface markers for T regulatory cells, the prognostic role and immune-related effects of CD39 in luminal breast cancer (BC) patients has not been evaluated yet. The aim of the current study was to explore the association between CD39 expression and clinic pathological characteristics and the prognosis in luminal BC patients.MethodsClinical information and RNA-sequencing (RNA-Seq) expression data were extracted from The Cancer Genome Atlas (TCGA). Patients were divided into a high or low CD39 expression group by the optimal cutoff value (4.18) identified from the receiver operating characteristic curve analysis. The relationships between CD39 expression and clinic pathological features were evaluated by the corresponding statistical tests. Survival analyses were applied to evaluate the overall survival between the high and low CD39 expression groups in luminal BC. Furthermore, Gene Expression Omnibus datasets were used for external data validation. Gene set enrichment analysis (GSEA) was also performed, and CIBERSORT was used to analyze the immune cell populations.ResultsAnalysis of 439 cases of tumor data showed that CD39 was overexpressed in luminal BC. The multivariable analysis suggested that CD39 expression was an independent prognostic factor for luminal BC patients. GSEA suggested that CD39 might play an important role in luminal BC progression through immune regulation. Analysis of immune cell patterns revealed high CD39 expression correlated to a higher proportion of CD8+ T cells and M2 macrophages.ConclusionThis study demonstrates that CD39 expression correlates with the prognosis of luminal BC through TCGA database mining. Further studies are warranted further to elucidate this potential novel therapeutic strategy for BC.

Multivariate analyses of MRI findings for predicting osteomyelitis of the foot in diabetic patients

2020 ◽  
Vol 61 (9) ◽  
pp. 1205-1212
Author(s):  
Yong-ho Jang ◽  
Sunghoon Park ◽  
Young Uk Park ◽  
Kyu-Sung Kwack ◽  
Seong Woo Jeon ◽  
...  
Keyword(s):  
Diabetic Foot ◽  
Signal Intensity ◽  
Multivariate Analyses ◽  
Characteristic Curve ◽  
Multivariable Analysis ◽  
Area Under The Curve ◽  
Intensity Change ◽  
Diabetic Patients ◽  
Mri Findings ◽  
Deep Ulcer

Background There have been no previous magnetic resonance imaging (MRI) studies using multivariable analysis to diagnose osteomyelitis in patients with diabetic foot. Purpose To retrospectively investigate the MRI findings of osteomyelitis in patients with diabetic foot using multivariate analyses. Material and Methods From November 2015 to March 2018, 118 patients who underwent MRI of the foot to evaluate suspected osteomyelitis were included in this study. The patients were categorized into the presence or absence of osteomyelitis. The primary and secondary MRI findings were retrospectively reviewed. To identify independent predictive MRI findings, multivariate analyses with binary logistic regression and receiver operating characteristic curve analyses were performed including all 118 patients and 93 patients presenting decreased T1 signal intensity, respectively. Results T1 signal intensity, T1 marrow pattern, T1 marrow distribution, T2 signal intensity, concordance of marrow signal intensity, cortical interruption, ulcer depth, abscess, and wet gangrene were significantly different between the two groups ( P < 0.05). Multivariate analyses indicated that fluid equivalent T2 signal intensity, deep ulcer, and confluent T1 marrow pattern were major factors associated with osteomyelitis. The area under the curve of predicted probabilities for the combination of these factors was 0.799 across all 118 patients and 0.761 across 93 patients with decreased T1 signal intensity. Conclusion Confluent T1 marrow pattern is a reliable finding to suggest osteomyelitis in patients with diabetic foot. In addition, fluid equivalent T2 signal intensity and deep ulcer are important findings that may suggest osteomyelitis, irrespective of T1 signal intensity change.

Discriminating Malignancy in Thyroid Nodules: The Nomogram Versus the Kwak and ACR TI-RADS

2020 ◽  
Vol 163 (6) ◽  
pp. 1156-1165
Author(s):  
Juan Xiao ◽  
Qiang Xiao ◽  
Wei Cong ◽  
Ting Li ◽  
Shouluan Ding ◽  
...  
Keyword(s):  
Thyroid Nodules ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Diagnostic Study ◽  
Diagnostic Efficiency ◽  
Training Set ◽  
Multivariable Logistic Regression Model ◽  
Predictive Values ◽  
Validation Set ◽  
Sensitivity Specificity

Objective To develop an easy-to-use nomogram for discrimination of malignant thyroid nodules and to compare diagnostic efficiency with the Kwak and American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS). Study Design Retrospective diagnostic study. Setting The Second Hospital of Shandong University. Subjects and Methods From March 2017 to April 2019, 792 patients with 1940 thyroid nodules were included into the training set; from May 2019 to December 2019, 174 patients with 389 nodules were included into the validation set. Multivariable logistic regression model was used to develop a nomogram for discriminating malignant nodules. To compare the diagnostic performance of the nomogram with the Kwak and ACR TI-RADS, the area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative predictive values were calculated. Results The nomogram consisted of 7 factors: composition, orientation, echogenicity, border, margin, extrathyroidal extension, and calcification. In the training set, for all nodules, the area under the curve (AUC) for the nomogram was 0.844, which was higher than the Kwak TI-RADS (0.826, P = .008) and the ACR TI-RADS (0.810, P < .001). For the 822 nodules >1 cm, the AUC of the nomogram was 0.891, which was higher than the Kwak TI-RADS (0.852, P < .001) and the ACR TI-RADS (0.853, P < .001). In the validation set, the AUC of the nomogram was also higher than the Kwak and ACR TI-RADS ( P < .05), each in the whole series and separately for nodules >1 or ≤1 cm. Conclusions When compared with the Kwak and ACR TI-RADS, the nomogram had a better performance in discriminating malignant thyroid nodules.

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