scholarly journals Using a gene expression signature when controversy exists regarding the indication for adjuvant systemic treatment reduces the proportion of patients receiving adjuvant chemotherapy: a nationwide study

2015 ◽  
Vol 18 (7) ◽  
pp. 720-726 ◽  
Author(s):  
A. Kuijer ◽  
A. C. M. van Bommel ◽  
C. A. Drukker ◽  
M. van der Heiden-van der Loo ◽  
C. H. Smorenburg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adjuvant Chemotherapy ◽  
Systemic Treatment ◽  
Gene Expression Signature ◽  
Nationwide Study ◽  
Expression Signature ◽  
Adjuvant Systemic Treatment

A 15-gene expression signature prognostic for survival and predictive for adjuvant chemotherapy benefit in JBR.10 patients

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 7510-7510 ◽  
Author(s):  
M. S. Tsao ◽  
C. Zhu ◽  
K. Ding ◽  
D. Strumpf ◽  
M. Pintilie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adjuvant Chemotherapy ◽  
Gene Expression Signature ◽  
Expression Signature

Prognostic and predictive effects of a gene expression signature for NRF2 pathway activation in lung squamous cell carcinoma (SqCC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7517-7517
Author(s):  
David W. Cescon ◽  
Desmond She ◽  
ChangQi Zhu ◽  
Shingo Sakashita ◽  
Melania Pintilie ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adjuvant Chemotherapy ◽  
Gene Expression Signature ◽  
Phase Iii ◽  
Nrf2 Pathway ◽  
Expression Signature ◽  
Prognostic Effect ◽  
Pathway Activation ◽  
Somatic Alterations ◽  
Mutational Activation

7517 Background: Genomic profiling of SqCC in TCGA identified somatic alterations that activate the NRF2 transcriptional program – a master regulator of the oxidative stress response – in ~35% of tumors (NFE2L2 mutations/amplifications, KEAP1 or CUL3 mutations/deletions). This pathway has been implicated in resistance to chemotherapy. To evaluate the clinical significance of this molecular subset, we developed a gene expression classifier and tested this signature as a predictor of adjuvant chemotherapy benefit with cisplatin/vinorelbine (cis/vin) in a subset of SqCC patients with microarray data from the NCIC JBR.10 Phase III clinical trial. Methods: Logistic regression (LR) and SAM analysis were independently applied to 104 TCGA SqCC cases that had both microarray gene expression and mutation data to identify genes associated with NRF2 pathway mutational status. Overlapping genes were used to define the signature, which was then tested in 3 independent SqCC datasets (62 JBR.10; 54 UHN; 129 UM) to evaluate the prognostic and predictive values of putative NRF2 pathway activation. Results: 29 genes comprising the signature were identified by overlap between LR (291 genes) and SAM (45 genes). The signature consistently separated SqCC into 2 groups in all datasets, corresponding to putatively activated and wild type (WT) NRF2 pathway tumors. No prognostic effect of the activated signature was observed in independent datasets (UHN HR 0.86, 95%CI 0.28 – 2.67; UM HR 1.43, 95%CI 0.82 – 2.48). Similarly, in JBR10, no prognostic effect was observed in the observation arm (n=24, HR 0.66, 95%CI 0.13 – 3.29). A trend toward improved survival with adjuvant chemotherapy was observed in patients with the WT signature (HR 0.34, 95%CI 0.08 – 1.78, p=0.13), but not in patients with the activated signature (HR 1.16, 95%CI 0.19 – 6.97, p=0.87; interaction p=0.18). Conclusions: A gene expression signature based on mutational activation of the NRF2 pathway may be predictive of benefit from adjuvant cis/vin in SqCC. Patients with NRF2 pathway activating somatic alterations may have reduced benefit from this therapy. Validation of this potentially "actionable" finding in additional datasets is necessary.

Association of YAP1 activation with poor patient prognosis and effect on chemoresistance in gastric cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4113-4113
Author(s):  
Sung Sook Lee ◽  
Sang Cheul Oh ◽  
Woojin Jeong ◽  
Sang Ho Lee ◽  
Sang-Bae Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Therapeutic Target ◽  
Notch Pathway ◽  
Gene Expression Signature ◽  
Expression Signature ◽  
Tumor Subtypes ◽  
Attractive Therapeutic Target ◽  
Patient Prognosis

4113 Background: Clinical heterogeneity in gastric cancer is likely due to biological differences among patients. Molecular subtypes and their associated biomarkers need to be established to improve treatment of this disease. We aimed to uncover subgroups of gastric cancer that have distinct biological characteristics associated with clinical outcome and to identify potential best treatments or therapeutic targets for each subgroup. Methods: We analyzed gene expression profiling data from gastric cancer cell lines and 267 patients with gastric cancer to uncover tumor subtypes and identify a gene expression signature associated with prognosis and response to adjuvant chemotherapy. The association of the signature with prognosis was validated in an independent cohort of 200 patients, and its association with response to adjuvant therapy was validated by cell culture experiments. Results: We identified an expression signature of 88 genes that specifically reflected activation of the oncogene YAP1. Compared with patients without this signature, patients with the YAP1 signature had significantly poorer prognosis. In multivariate analysis, the signature was the strongest indicator of overall survival among all demographic and clinical variables examined together (hazard ratio, 2.1; 95% confidence interval, 1.3-3.3;P = .002). Activation of YAP1 was significantly associated with resistance to adjuvant chemotherapy. We also demonstrated that the Notch pathway is a potential therapeutic target for overcoming chemoresistance mediated by YAP1. Conclusions: Activation of the oncogene YAP1 is significantly associated with poorer survival of patients with gastric cancer and induces chemoresistance to this disease. Therefore, YAP1 may be highly attractive therapeutic target for patients with gastric cancer resistant to standard chemotherapy.

A prognostic eight‐gene expression signature for patients with breast cancer receiving adjuvant chemotherapy

2019 ◽  
Vol 121 (8-9) ◽  
pp. 3923-3934 ◽  
Author(s):  
Qiuxia Cui ◽  
Jianing Tang ◽  
Dan Zhang ◽  
Deguang Kong ◽  
Xing Liao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Adjuvant Chemotherapy ◽  
Gene Expression Signature ◽  
Expression Signature

scholarly journals Gene-expression signature of tumor recurrence in patients with stage II and III colon cancer treated with 5′fluoruracil-based adjuvant chemotherapy

2012 ◽  
Vol 132 (5) ◽  
pp. 1090-1097 ◽  
Author(s):  
María Dolores Giráldez ◽  
Juan José Lozano ◽  
Míriam Cuatrecasas ◽  
Virginia Alonso-Espinaco ◽  
Joan Maurel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Tumor Recurrence ◽  
Gene Expression Signature ◽  
Stage Ii ◽  
Expression Signature

scholarly journals Cytotoxic T-cell-related gene expression signature predicts improved survival in muscle-invasive urothelial bladder cancer patients after radical cystectomy and adjuvant chemotherapy

2020 ◽  
Vol 8 (1) ◽  
pp. e000162 ◽  
Author(s):  
Markus Eckstein ◽  
Pamela Strissel ◽  
Reiner Strick ◽  
Veronika Weyerer ◽  
Ralph Wirtz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Adjuvant Chemotherapy ◽  
Immune Status ◽  
Survival Rates ◽  
Gene Expression Signature ◽  
Cancer Center ◽  
Expression Signature ◽  
Platinum Based Chemotherapy ◽  
Muscle Invasive

BackgroundAssessment of the immune status of muscle-invasive bladder cancer (MIBC) has previously shown to be prognostically relevant after treatment with curative intent. We conducted this study to develop a clinically applicable immune gene expression assay to predict prognosis and adjuvant chemotherapy benefit.Patients and methodsGene expression ofCD3Z,CD8AandCXCL9, immune cell (IC) populations including stromal tumor infiltrating lymphocytes (sTILs), T-cells, natural killer cells (NK-cells), macrophages, Programmed cell death protein 1 positive (PD-1) IC and tumor subtypes (MD Anderson Cancer Center/MDACC-approach) were assessed in 187 MIBC patients (Comprehensive Cancer Center Erlangen-EMN/CCC-EMN-cohort). A gene expression signature was derived by hierarchical-clustering and validated in The Cancer Genome Atlas (TCGA)-cohort. IC populations in the TCGA cohort were assessed via CIBERSORT. Benefit of platinum-containing adjuvant chemotherapy was assessed in a pooled cohort of 125 patients. Outcome measurements were disease specific survival, disease-free survival and overall survival.ResultsThe gene expression signature ofCXCL9,CD3ZandCD8Acorrelates with quantitative amounts of specific IC populations and sTILs (CCC-EMN: ρ-range: 0.44–0.74; TCGA: ρ-range: 0.56–0.82) and allows stratification of three different inflammation levels (inflamed high, inflamed low, uninflamed). Highly inflamed tumors are preferentially basal subtype and show favorable 5-year survival rates of 67.3% (HR=0.27; CCC-EMN) and 55% (HR=0.41; TCGA). Uninflamed tumors are predominantly luminal subtypes and show low 5-year survival rates of 28% (CCC-EMN) and 36% (TCGA). Inflamed tumors exhibit higher levels of PD-1 and Programmed cell death 1 ligand 1 (PD-L1). Patients undergoing adjuvant platinum-based chemotherapy with ‘inflamed high’ tumors showed a favorable 5-year survival rate of 64% (HR=0.27; merged CCC-EMN and TCGA cohort).ConclusionThe gene expression signature ofCD3Z,CD8AandCXCL9can assess the immune status of MIBC and stratify the survival of MIBC patients undergoing surgery and adjuvant platinum-based chemotherapy. Furthermore, the assay can identify patients with immunological hot tumors with particular high expression of PD-L1 potentially suitable for immunotherapy.

Sign in / Sign up

Export Citation Format

Share Document