59831ec7-7e89-4575-8c30-c3e8d2faeec7 - samples
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ABSTRACT:
PROVIDER: EGAD00001008157 | EGA |
REPOSITORIES: EGA
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Project description:The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival (DFS) of resected EGFR-mutant stage II-IIIA non-small cell lung cancer (NSCLC). However, not all patients experienced favorable clinical outcomes with TKI, raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.
| EGAS00001005632 | EGA
Project description:Eighty-four completely resected stage I/II non-small cell lung cancer (NSCLC) without adjuvant therapy were profiled using whole genome expression microarrys in order to identify novel classifications associated with RFS. Association with relapse-free survival (RFS) and clinicopathological parameters was assessed. An external cohort of 162 tumors was used to validate results.
2014-07-29 | E-MTAB-1790 | biostudies-arrayexpress
Project description:Introduction: Effective predictive biomarkers for selection of patients benefiting from adjuvant platinum-based chemotherapy in non-small cell lung cancer (NSCLC) are needed. Based on a previously validated methodology, molecular profiles of predicted sensitivity in two patient cohorts are presented. Methods: The profiles are correlations between in vitro sensitivity to cisplatin and vinorelbine and baseline mRNA expression of the 60 cell lines in the National Cancer Institute panel. An applied clinical samples filter focused the profiles to clinically relevant genes. The profiles were tested on 1) snap-frozen tumors from 133 patients with completely resected stage 1B-2 NSCLC randomized to adjuvant cisplatin and vinorelbine (ACV, n=71) or no adjuvant treatment (OBS, n=62) [GSE14814] and 2) formalin-fixed paraffin-embedded (FFPE) pre-treatment tumors from 95 patients with completely resected stage 1A-3B NSCLC receiving adjuvant cisplatin and vinorelbine. Results: The combined cisplatin and vinorelbine profiles showed: 1) univariate Hazard Ratio (HR) for sensitive versus resistant of 0.265 (95% CI:0.079-0.889, p=0.032) in the ACV cohort and a HR of 0.28 in a multivariate model (95% CI:0.08-1.04, p=0.0573); 2) significant prediction at 3 year survival from surgery in univariate (HR=0.138 (95% CI:0.035-0.537), p=0.004) and multivariate analysis (HR=0.14 (95% CI:0.030-0.6), p=0.0081). No discrimination was found in the OBS cohort (HR=1.328, p=0.60). The cisplatin predictor alone had similar figures with 1) univariate HR of 0.37 (95% CI:0.12-1.15, p=0.09) in the ACV cohort and 2) univariate HR of 0.14 (95% CI:0.03-0.59, p=0.0076) to three years. Functional analysis on the cisplatin profile revealed a group of upregulated genes related to RNA splicing as a part of DNA damage repair and apoptosis. Conclusions: Profiles derived from snap-frozen and FFPE NSCLC tissue were prognostic and predictive in the patients that received cisplatin and vinorelbine but not in the cohort that did not receive adjuvant treatment.
2017-12-25 | GSE108492 | GEO
Project description:Purpose: The JBR.10 trial demonstrated benefit from adjuvant cisplatin/vinorelbine (ACT) in early-stage non-small-cell lung cancer (NSCLC). We hypothesized that expression profiling may identify stage-independent subgroups who might benefit from ACT. Patients and Methods: Gene expression profiling was conducted on mRNA from 133 frozen JBR.10 tumor samples (62 observation [OBS], 71 ACT). The minimum gene set that was selected for the greatest separation of good and poor prognosis patient subgroups in OBS patients was identified. The prognostic value of this gene signature was tested in four independent published microarray data sets and by quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR). Results: A 15-gene signature separated OBS patients into high-risk and low-risk subgroups with significantly different survival (hazard ratio [HR], 15.02; 95% CI, 5.12 to 44.04; P .001; stage I HR, 13.31; P .001; stage II HR, 13.47; P .001). The prognostic effect was verified in the same 62 OBS patients where gene expression was assessed by qPCR. Furthermore, it was validated consistently in four separate microarray data sets (total 356 stage IB to II patients without adjuvant treatment) and additional JBR.10 OBS patients by qPCR (n 19). The signature was also predictive of improved survival after ACT in JBR.10 high-risk patients (HR, 0.33; 95% CI, 0.17 to 0.63; P .0005), but not in low-risk patients (HR, 3.67; 95% CI, 1.22 to 11.06; P = .0133; interaction P .001). Significant interaction between risk groups and ACT was verified by qPCR. Conclusion: This 15-gene expression signature is an independent prognostic marker in early-stage, completely resected NSCLC, and to our knowledge, is the first signature that has demonstrated the potential to select patients with stage IB to II NSCLC most likely to benefit from adjuvant chemotherapy with cisplatin/vinorelbine.
2010-09-09 | GSE14814 | GEO
Project description:To date, the 5-year overall survival of early-stage non-small cell lung cancer (NSCLC) is still unsatisfactory at 59.8%. Therefore, reliable prognostic factors are needed. Growing evidence shows that cancer progression may depend on a double interconnection between cancer cells and the surrounding tumor microenvironment; hence, circulating molecules may represent promising markers of cancer recurrence. Here, we performed in-depth analysis of circolome-derived markers, including Exo-miRnome and peptidome in 67 radically resected NSCLCs, to identify a prognostic score. The miRnome profile selected exo-miR130a-3p as the most overexpressed in patients with relapse. Peptidome analysis identified 4 progressively more degraded forms of fibrinopeptide A (fpA) in progressing patients. Notably, the combination of exo-miR130a-3p and the greatest fpA (2-16) built a score where high-risk patients had 24 months of disease-free survival. Moreover, in vitro transfections showed that higher levels of exo-miR-130a-3p lead to a deregulation of some pathways involved in metastasis, in angiogenesis, such as in coagulation which could be linked to the FpA reduction. In conclusion, the identified risk score integrating circulating markers can help clinicians predict early-stage NSCLC patients who are more likely to relapse after initial surgery.
2022-03-16 | MSV000089072 | MassIVE
Project description:Study to identify genes associated with NSCLC recurrence in patients not receiving adjuvant chemotherapy. Purpose: Recent clinical trials suggest improvement in survival with adjuvant chemotherapy in non-small cell lung cancer (NSCLC). This study's aim is to identify genes associated with NSCLC recurrence in patients not receiving adjuvant chemotherapy. Experimental design: Banked NSCLC tumors of patients who underwent resection of stage Ia-IIIb disease were identified. Patients were stratified into two groups: recurrent (R, n=11) or non-recurrent (NR, n=16) 2 years after surgery. Microarray profiling and Cox multivariate analysis were performed. Conclusion: Increased CYP3A5 gene expression correlates with NSCLC recurrence and promotes proliferation through mechanisms that may involve, in part, CYP3A5 epoxygenase activity. Experiment Overall Design: comparison of gene expression profiles for recurrent and non-recurrent cancer
2009-12-14 | E-GEOD-9971 | biostudies-arrayexpress
Project description:Understanding the molecular events in non-small cell lung cancer (NSCLC) is essential to improve early diagnosis and treatment for this disease. We examined the effect of chromosomal copy number changes on gene expression in resected NSCLC patients. We identified a deletion on 14q32.2-33 as a common alteration in NSCLC (44%), which significantly influenced gene expression for HSP90AA1, residing on 14q32. This deletion was correlated with better overall and recurrence free survival (P=0.008 and P=0.004, respectively) and survival was also longer in patients whose tumors had low expression levels of HSP90AA1. We extended the analysis to an independent validation set of 140 resected NSCLC patients, and confirmed low HSP90AA1 expression to be significantly related with overall survival and recurrence free survival (P=0.003 and P=0.007, respectively). In vitro treatment with an HSP90 inhibitor had potent antiproliferative activity in NSCLC cell lines. We suggest that targeting HSP90 will have clinical impact for NSCLC patients. Keywords: Array CGH gene expression integration
2007-08-01 | GSE7878 | GEO
Project description:Analysis of gefitinib short-term resistance at gene expression level. The hyposthesis tested in the present study was that short-term resistance towards gefitinib in NSCLC cells influences pathways that associates with resistance towards EGFR-TKI treatment. Results provide important information of the response of EGFR mutant NSCLC cells to gefitinib and also to resistance towards gefitinib resistance, up-or down-regulated specific resistance pathways and cellular functions. Total RNA obtained from HCC827 cell line (n=3), co-cultured HCC827 (with MRC-5 cells)(n=3), gefitinib treated (0.5µM) HCC827 (n=3), and co-cultured (MRC-5) + gefitinib treated HCC827 cells (n=3) for 48h after gefitinib treatment
2016-07-01 | E-GEOD-75307 | biostudies-arrayexpress
Project description:Analysis of gefitinib short-term resistance at gene expression level. The hyposthesis tested in the present study was that short-term resistance towards gefitinib in NSCLC cells influences pathways that associates with resistance towards EGFR-TKI treatment. Results provide important information of the response of EGFR mutant NSCLC cells to gefitinib and also to resistance towards gefitinib resistance, up-or down-regulated specific resistance pathways and cellular functions. Total RNA obtained from PC9 cell line (n=3), co-cultured PC9 (with MRC-5 cells)(n=3), gefitinib treated (0.5µM) PC9 (n=3), and co-cultured (MRC-5) + gefitinib treated PC9 cells (n=3) for 48h after gefitinib treatment
2016-07-01 | E-GEOD-75308 | biostudies-arrayexpress
Project description:To date, the 5-year overall survival of early stage non-small cell lung cancer (NSCLC) is still unsatisfactory at 59.8%. Therefore, reliable prognostic factors are needed. Growing evidence shows that cancer progression may depend on a double interconnection between cancer cells and the surrounding tumor microenvironment, and circulating molecules may represent promising markers of cancer recurrence. Here, we performed in-depth analysis of circolome-derived markers, including Exo-miRnome and peptidome in 67 radically resected NSCLCs, to identify a prognostic score. The miRnome profile selected exo-miR130a-3p as the most overexpressed in patients with relapse. Peptidome analysis identified 4 fibrinopeptide A (fpA), which were depleted in progressing patients. Notably, the combination of exo-miR130a-3p and the greatest fpA (2-16) built a score where high-risk patients had 24 months of disease-free survival. Moreover, in vitro transfections showed that higher levels of exo-miR-130a-3p lead to a deregulation of some pathways involved in metastasis, in angiogenesis, such as in coagulation. In conclusion, the identified risk score integrating circulating markers can help clinicians predict early-stage NSCLC patients who are more likely to relapse after initial surgery.
2022-05-01 | GSE198958 | GEO