scholarly journals P67. Pretherapeutical gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy and its impact on disease free survival

2006 ◽  
Vol 4 (6) ◽  
pp. 51-52
Author(s):  
Marian Grade ◽  
Torsten Liersch ◽  
Sudhir Varma ◽  
Michael J. Difilippantonio ◽  
Claus Langer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Disease Free Survival ◽  
Response Prediction ◽  
Preoperative Chemoradiotherapy ◽  
Free Survival ◽  
Disease Free

Prediction of Disease-free Survival in Hepatocellular Carcinoma by Gene Expression Profiling

2013 ◽  
Vol 20 (12) ◽  
pp. 3747-3753 ◽  
Author(s):  
Ho-Yeong Lim ◽  
Insuk Sohn ◽  
Shibing Deng ◽  
Jeeyun Lee ◽  
Sin Ho Jung ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

scholarly journals Effectiveness of Gene Expression Profiling for Response Prediction of Rectal Adenocarcinomas to Preoperative Chemoradiotherapy

2005 ◽  
Vol 23 (9) ◽  
pp. 1826-1838 ◽  
Author(s):  
B. Michael Ghadimi ◽  
Marian Grade ◽  
Michael J. Difilippantonio ◽  
Sudhir Varma ◽  
Richard Simon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Response Prediction ◽  
Preoperative Chemoradiotherapy ◽  
Response To Therapy ◽  
Phase Iii ◽  
Correct Prediction

Purpose There is a wide spectrum of tumor responsiveness of rectal adenocarcinomas to preoperative chemoradiotherapy ranging from complete response to complete resistance. This study aimed to investigate whether parallel gene expression profiling of the primary tumor can contribute to stratification of patients into groups of responders or nonresponders. Patients and Methods Pretherapeutic biopsies from 30 locally advanced rectal carcinomas were analyzed for gene expression signatures using microarrays. All patients were participants of a phase III clinical trial (CAO/ARO/AIO-94, German Rectal Cancer Trial) and were randomized to receive a preoperative combined-modality therapy including fluorouracil and radiation. Class comparison was used to identify a set of genes that were differentially expressed between responders and nonresponders as measured by T level downsizing and histopathologic tumor regression grading. Results In an initial set of 23 patients, responders and nonresponders showed significantly different expression levels for 54 genes (P < .001). The ability to predict response to therapy using gene expression profiles was rigorously evaluated using leave-one-out cross-validation. Tumor behavior was correctly predicted in 83% of patients (P = .02). Sensitivity (correct prediction of response) was 78%, and specificity (correct prediction of nonresponse) was 86%, with a positive and negative predictive value of 78% and 86%, respectively. Conclusion Our results suggest that pretherapeutic gene expression profiling may assist in response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy. The implementation of gene expression profiles for treatment stratification and clinical management of cancer patients requires validation in large, independent studies, which are now warranted.

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.

A New Molecular Classification of Multiple Myeloma Using Gene Expression Profiling and Fluorescence In Situ Hybridisation as Predictor for Event Free Survival.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 73-73 ◽  
Author(s):  
Dirk Hose ◽  
Jean-Francois Rossi ◽  
Carina Ittrich ◽  
John deVos ◽  
Axel Benner ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Myeloma ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Molecular Classification ◽  
Differentially Expressed ◽  
Event Free Survival ◽  
Free Survival ◽  
Cytogenetic Aberrations

Abstract AIM was to establish a new molecular classification of Multiple Myeloma (MM) based on changes in global gene expression attributable to cytogenetic aberrations detected by interphase FISH (iFISH) in order to (i) predict event free survival (EFS) and (ii) investigate differentially expressed genes as basis for a group specific and risk adapted therapy. PATIENTS AND METHODS. Bone marrow aspirates of 105 newly diagnosed MM-patients (65 trial (TG) / 40 independent validation group (VG)) and 7 normal donors (ND) were CD138-purified by magnetic activated cell sorting. RNA was in-vitro transcribed and hybridised to Affymetrix HG U133 A+B GeneChip (TG) and HG U133 2.0 plus arrays (VG). CCND1 and CCND2 expression was verified by real time RT-PCR. iFISH was performed on purified MM-cells using probes for chromosomes 11q23, 11q13, 13q14, 17p13 and the IgH-translocations t(4;14) and t(11;14). Expression data were normalised (Bioconductor package gcrma) and nearest shrunken centroids (NSC) applied to calculate and cross validate a predictor on 40 patients of the TG with a comprehensive iFISH panel available combined with CCND overexpression. Differentially expressed genes were identified using empirical Bayes statistics for pairwise comparison. RESULTS. Overexpression of a D-type cyclin (D1 or D2) was found in 61/65 patients with MM compared to ND. CCND3 overexpression only appeared concomitantly with CCND2 overexpression. Four groups could be distinguished: (1.1) CCND1 (11q13) overexpression and trisomy 11q13, (1.2) CCND1 overexpression and translocations involving 11q13 i.e. t(11;14), (2.1) CCND2 overexpression without 11q13+, t(11;14), t(4;14), (2.2) CCND2 overexpression with t(4;14) and FGFR3 upregulation. A predictor of 6 to 566 genes correctly classifies all 40 patients of the TG (estimated cross validated error rate 0%). An independent VG of 40 patients was used. Genes with highest scores in NSC are: (1.1) CCND1, ribosomal proteins (e.g. RPL 28, 29), GPX1, CCRL2, (1.2) CCND1, TGIF, and NCAM (non-overexpression), (2.1) CCND2, (2.2) FGFR3, WHSC1, CCND2, IRTA2, SELL, and MAGED4. Distribution of clinical parameters (i.e. β2M, Durie Salmon stages, ISS) was not significantly different between the groups. The distribution of del(13)(q14q14) was (1.1) 31.5%, (1.2) 37.5%, (2.1) 37.5% and (2.2) 100%. (p<0.01). I.e. HGF, DKK1, VCAM, CD163 are differentially expressed between all 4 groups and ND (adjusted p<0.001). The groups defined by the predictor show a significantly different EFS after autologous stem cell transplantation according to the GMMG-HD3 protocol (median: (1.1) 18 / (1.2) not reached (no event) / (2.1) 22 / (2.2) 6 months; log-rank-test: p=0.004). CONCLUSION. CCND1 or CCND2 overexpression is nearly ubiquitous in MM and attributable to defined cytogenetic aberrations. Gene expression and iFISH allow a molecular classification of MM which can be predicted by gene expression profiling alone. Groups in the classification show a distinctive pattern in gene expression as well as a different EFS interpretable as risk stratification and indicator of therapeutic targets.

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