Gene Expression Profiling Reveals a New Classification of Adrenocortical Tumors and Identifies Molecular Predictors of Malignancy and Survival

2009 ◽  
Vol 27 (7) ◽  
pp. 1108-1115 ◽  
Author(s):  
Aurélien de Reyniès ◽  
Guillaume Assié ◽  
David S. Rickman ◽  
Frédérique Tissier ◽  
Lionel Groussin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Validation Cohort ◽  
Malignant Tumors ◽  
Disease Free Survival ◽  
Free Survival ◽  
Training Cohort ◽  
Adrenocortical Tumors ◽  
Independent Validation ◽  
Gene Predictor ◽  
Disease Free

Purpose Adrenocortical tumors, especially cancers, remain challenging both for their diagnosis and prognosis assessment. The aim of this article is to identify molecular predictors of malignancy and of survival. Patients and Methods One hundred fifty-three unilateral adrenocortical tumors were studied by microarray (n = 92) or reverse transcription quantitative polymerase chain reaction (n = 148). A two-gene predictor of malignancy was built using the disease-free survival as the end point in a training cohort (n = 47), then validated in an independent validation cohort (n = 104). The best candidate genes were selected using Cox models, and the best gene combination was validated using the log-rank test. Similarly, for malignant tumors, a two-gene predictor of survival was built using the overall survival as the end point in a training cohort (n = 23), then tested in an independent validation cohort (n = 35). Results Unsupervised clustering analysis discriminated robustly the malignant and benign tumors, and identified two groups of malignant tumors with very different outcome. The combined expression of DLG7 and PINK1 was the best predictor of disease-free survival (log-rank P ≈ 10−12), could overcome the uncertainties of intermediate pathological Weiss scores, and remained significant after adjustment to the Weiss score (P < 1.3 × 10−2). Among the malignant tumors, the combined expression of BUB1B and PINK1 was the best predictor of overall survival (P < 2 × 10−6), and remained significant after adjusting for MacFarlane staging (P < .005). Conclusion Gene expression analysis unravels two distinct groups of adrenocortical carcinomas. The molecular predictors of malignancy and of survival are reliable and provide valuable independent information in addition to pathology and tumor staging. These original tools should provide important improvements for adrenal tumors management.

scholarly journals Development and Validation of a Prognostic Nomogram in Patients with Bladder Cancer after Radical Cystectomy: A Study Based on the Chinese Population

2021 ◽  
Author(s):  
Xun Lu ◽  
Yiduo Wang ◽  
Qi Chen ◽  
Di Xia ◽  
Hanyu Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Validation Cohort ◽  
Disease Free Survival ◽  
Calibration Plot ◽  
Concordance Index ◽  
Free Survival ◽  
Training Cohort ◽  
Disease Free

Abstract PurposeTo develop and validate a prognostic nomogram in patients with bladder cancer who underwent radical cystectomy based on the Chinese population.MethodsThe nomogram was built on a retrospective study included 191 patients with bladder cancer who underwent radical cystectomy between January 2010 to December 2019 at the authors’ hospital. The primary cohort was divided into the training cohort and the validation cohort randomly. The endpoints in the study were disease-free survival and overall survival. The ability of distinguishing and predicting of the prognostic nomogram were determined by calibration plot and concordance index in the training cohort. Moreover, the results were also verified in the validation cohort internally.ResultsMultivariate analysis of the training cohort showed that hydronephrosis, Stage_T, Stage_N, PNI and EGFR were significantly associated with overall survival. Meanwhile, Stage_T, Stage_N, PNI and EGFR were independent risk factors for disease-free survival. The calibration plot agreed well between prediction and actual observation in survival possibility. The concordance index of the nomogram in the training cohort of overall survival and disease-free survival were 0.834 (95%CI: 0.785-0.833) and 0.823 (95%CI: 0.772-0.873), respectively. In the validation cohort, the nomogram also showed high predictive accuracy.ConclusionThe proposed nomogram showed high accuracy in predicting survival for bladder cancer patients after radical cystectomy.

Six-gene model based on expression predicts distinct disease-free survival in early-stage microsatellite stability (MSS) endometrial, colorectal and stomach tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14578-e14578
Author(s):  
Tufeng Chen ◽  
Jianpei Liu ◽  
Xinyi Liu ◽  
Mengli Huang
Keyword(s):  
Immune Cells ◽  
Validation Cohort ◽  
Early Stage ◽  
Disease Free Survival ◽  
Low Risk ◽  
Rna Seq ◽  
Free Survival ◽  
Training Cohort ◽  
Microsatellite Stability ◽  
Disease Free

e14578 Background: Microsatellite stability (MSS) tumors hardly benefit from immunotherapies and are more probable to occur postoperative recurrence. However, some studies have revealed that a subset of MSS patients harbor “hot immune microenvironment” tumors, indicating high heterogeneity in such wide range of patient population. On the other hand, researches of mechanism of MSI formation found potential similarities in endometrial and gastrointestinal tumors. We hypothesized the transcriptomic features in these cancers correlated with immune-related signatures and patients’ prognosis. Methods: Early stage (I-III stage) MSS tumors, including endometrial, colorectal, and gastric from TCGA project were analyzed as training cohort (n=170). A combined cohort consisting of 604 colorectal and stomach cancers from GEO datasets (GSE39582，GSE62254) was validation cohort. The RNA-Seq profiling data and disease-free survival (DFS) data of patients were collected. Cibersort tool was used to evaluate twenty-two immune cells’ enrichment. The prediction model was developed by three steps: Univariate cox regression of DFS was conducted to select 9 immune cells. Then the train cohort was divided into two groups based on non-negative matrix factorization (NMF) method using this 9 immune cell features. Differentially expressed genes of these two groups were identified and screened further by lasso regression. Log-rank test was used to evaluate the difference of DFS. Results: A six-gene lasso-cox model was developed. The genes were LYZ, WFDC2, CAPS, RHPN1, TFF2 and TGFBR2. Based on the score evaluated by this model, patients in training cohort were divided into high-risk and low-risk groups. Low-risk population had much longer DFS (HR 0.07, 95%CI 0.03-0.18, p<0.001). In validation cohort, lower risk score was also verified to be associated with a lower likelihood of recurrence (HR 0.66, 95%CI 0.5-0.88, p=0.0047). Conclusions: We developed a model of six-genes predicting disease-free survival based on RNA-Seq data in early stage MSS patients. Further validation was needed to implement in larger clinical cohorts.

scholarly journals Prognostic implications of programmed death ligand 1 expression in resected lung adenocarcinoma: a systematic review and meta-analysis

2020 ◽  
Vol 58 (5) ◽  
pp. 888-898
Author(s):  
Donglai Chen ◽  
Yiming Mao ◽  
Qifeng Ding ◽  
Wei Wang ◽  
Feng Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Lung Adenocarcinoma ◽  
Messenger Rna ◽  
Disease Free Survival ◽  
Pooled Analysis ◽  
The Cancer Genome Atlas ◽  
Free Survival ◽  
L1 Protein ◽  
Disease Free

Abstract OBJECTIVES Conflicting results have been reported about the prognostic value of programmed death ligand 1 (PD-L1) protein and gene expression in lung adenocarcinoma. METHODS We performed a comprehensive online search to explore the association between PD-L1 expression (protein and messenger RNA) and overall survival (OS) or disease-free survival. Outcomes also included pooled rates of high PD-L1 protein expression in different cell types, per threshold used and per antibody used. A pooled gene expression analysis was also performed on 3 transcriptomic data sets that were obtained from The Cancer Genome Atlas database and the Gene Expression Omnibus database. RESULTS A total of 6488 patients from 25 studies were included. The pooled results suggested that high PD-L1 expression was associated with shorter OS [hazard ratio (HR) 1.57; P &lt; 0.001] and disease-free survival (HR 1.341; P = 0.037) in the overall population. The overall pooled rate of high PD-L1 protein expression was 29% (95% confidence interval 23–34%) in tumour cells. In subgroup analysis, high PD-L1 protein expression in tumour cells predicted worse OS and disease-free survival. A pooled analysis of The Cancer Genome Atlas and Gene Expression Omnibus data sets revealed that higher levels of PD-L1 messenger RNA predicted poorer OS in the entire population. CONCLUSIONS This study is, to our knowledge, the largest pooled analysis on the subject to shed light on the high expression rate of PD-L1 and the prognostic value of high PD-L1 expression in resected lung adenocarcinomas. PD-L1 gene expression is a promising prognostic factor for patients with surgically resected lung adenocarcinoma. Standardization of staining should be underscored prior to routine implementation.

DNA copy number alterations, gene expression changes and disease-free survival in patients with colorectal cancer: a 10 year follow-up

2016 ◽  
Vol 39 (6) ◽  
pp. 545-558 ◽  
Author(s):  
Elisabetta Bigagli ◽  
Carlotta De Filippo ◽  
Cinzia Castagnini ◽  
Simona Toti ◽  
Francesco Acquadro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Copy Number ◽  
Disease Free Survival ◽  
Copy Number Alterations ◽  
Dna Copy Number ◽  
Free Survival ◽  
Dna Copy Number Alterations ◽  
Disease Free

EGR1 Predicts PTEN and Survival in Patients With Non–Small-Cell Lung Cancer

2005 ◽  
Vol 23 (9) ◽  
pp. 1921-1926 ◽  
Author(s):  
Bernadette Ferraro ◽  
Gerold Bepler ◽  
Swati Sharma ◽  
Alan Cantor ◽  
Eric B. Haura
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Tumor Suppressor ◽  
Small Cell Lung Cancer ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Disease Free

Purpose The zinc finger transcription factor early growth response gene 1 (EGR1) is underexpressed in non–small-cell lung cancer (NSCLC) compared with normal lung. EGR1 expression has been linked to tumor suppression as a result of cell cycle arrest and apoptosis through regulation of tumor suppressor pathways including PTEN. For these reasons, we hypothesized that reduced levels of EGR1 would correlate with inferior outcome in patients with NSCLC. Patients and Methods Patients who underwent surgical resection for NSCLC had RNA extracted from tumor tissue and EGR1 gene expression was quantified by real-time quantitative polymerase chain reaction. The levels of EGR1 expression were examined in relationship to patient characteristics, histology, tumor stage, PTEN expression, and overall and disease-free survival. Results EGR1 expression strongly correlated with PTEN expression (P < .0001). No correlation of EGR1 with histology or stage was detected. Patients with high levels of EGR1 had better overall and disease-free survival compared with patients with low levels of EGR1 (P = .040 and P = .096, respectively). In a stratified log-rank test, low EGR1 expression was predictive of poor survival independent of tumor stage. Conclusion EGR1 gene expression predicts PTEN levels and survival after surgical resection of NSCLC. Consistent with its known tumor suppressor properties, lower levels of EGR1 are associated with poor outcome. Identification of patients with low EGR1 therefore may identify patients at high risk for disease recurrence and may also identify patients who have tumors resistant to therapy secondary to loss of pathways such as PTEN.

scholarly journals CRITICAL EVALUATION OF LONG-TERM RESULTS OF MALIGNANT HEPATIC TUMORS TREATED BY MEANS CURATIVE LAPAROSCOPIC HEPATECTOMY

2017 ◽  
Vol 30 (3) ◽  
pp. 205-210 ◽  
Author(s):  
Sergio Renato PAIS-COSTA ◽  
Sergio Luiz Melo ARAÚJO ◽  
Olímpia Alves Teixeira LIMA ◽  
Sandro José MARTINS
Keyword(s):  
Overall Survival ◽  
Tumor Recurrence ◽  
Malignant Tumors ◽  
Laparoscopic Hepatectomy ◽  
Disease Free Survival ◽  
Long Term Results ◽  
Colorectal Metastases ◽  
Free Survival ◽  
Disease Free

ABSTRACT Background: Laparoscopic hepatectomy has presented great importance for treating malignant hepatic lesions. Aim: To evaluate its impact in relation to overall survival or disease free of the patients operated due different hepatic malignant tumors. Methods: Thirty-four laparoscopic hepatectomies were performed in 31 patients with malignant neoplasm. Patients were distributed as: Group 1 - colorectal metastases (n=14); Group 2 - hepatocellular carcinoma (n=8); and Group 3 - non-colorectal metastases and intrahepatic cholangiocarcinoma (n=9). The conversion rate, morbidity, mortality and tumor recurrence were also evaluated. Results: Conversion to open surgery was 6%; morbidity 22%; postoperative mortality 3%. There was tumor recurrence in 11 cases. Medians of overall survival and disease free survival were respectively 60 and 46 m; however, there was no difference among studied groups (p>0,05). Conclusion: Long-term outcomes of laparoscopic hepatectomy for treating hepatic malignant tumors are satisfactory. There is no statistical difference in relation of both overall and disease free survival among different groups of hepatic neoplasms.

Prediction of disease-free survival in gastric cancer using gene expression data

2003 ◽  
Vol 124 (4) ◽  
pp. A554-A555
Author(s):  
Alex Boussioutas ◽  
Ryan Van Laar ◽  
Paul Desmond ◽  
David Bowtell
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Gene Expression Data ◽  
Disease Free Survival ◽  
Expression Data ◽  
Free Survival ◽  
Disease Free

Radical mediastinal nodal removal improves disease-free survival for pulmonary low-grade malignant tumors

Lung Cancer ◽  
2012 ◽  
Vol 75 (3) ◽  
pp. 342-347 ◽  
Author(s):  
Hui Zheng ◽  
Hui-kang Xie ◽  
Chao Li ◽  
Fang Bao ◽  
Jia-an Ding ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Disease Free Survival ◽  
Low Grade ◽  
Free Survival ◽  
Disease Free

scholarly journals A Five-Gene Prognostic Nomogram Predicting Disease-Free Survival of Differentiated Thyroid Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Pan Ruchong ◽  
Tang Haiping ◽  
Wang Xiang
Keyword(s):  
Gene Expression ◽  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Disease Free Survival ◽  
Gene Signature ◽  
Training Dataset ◽  
Prediction Ability ◽  
Free Survival ◽  
Testing Dataset ◽  
Disease Free

Background. Differentiated thyroid cancer (DTC) is the most common type of thyroid tumor with a high recurrence rate. Here, we developed a nomogram to effectively predict postoperative disease-free survival (DFS) in DTC patients. Methods. The mRNA expressions and clinical data of DTC patients were downloaded from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Seventy percent of patients were randomly selected as the training dataset, and thirty percent of patients were classified into the testing dataset. Multivariate Cox regression analysis was adopted to establish a nomogram to predict 1-year, 3-year, and 5-year DFS rate of DTC patients. Results. A five-gene signature comprised of TENM1, FN1, APOD, F12, and BTNL8 genes was established to predict the DFS rate of DTC patients. Results from the concordance index (C-index), area under curve (AUC), and calibration curve showed that both the training dataset and the testing dataset exhibited good prediction ability, and they were superior to other traditional models. The risk score and distant metastasis (M) of the five-gene signature were independent risk factors that affected DTC recurrence. A nomogram that could predict 1-year, 3-year, and 5-year DFS rate of DTC patients was established with a C-index of 0.801 (95% CI: 0.736, 0.866). Conclusion. Our study developed a prediction model based on the gene expression and clinical characteristics to predict the DFS rate of DTC patients, which may be applied to more accurately assess patient prognosis and individualized treatment.

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