Identification of molecular signatures associated with early relapse after complete resection of lung adenocarcinomas
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE132690 | GEO | 2021/05/26
REPOSITORIES: GEO
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Project description:Identification of molecular signatures associated with early relapse after complete resection of lung adenocarcinomas
| PRJNA548775 | ENA
Project description:The only potentially curative treatment for lung adenocarcinoma patients remains complete resection of early-stage tumors. However, many patients develop recurrence and die of their disease despite curative surgery. Underlying mechanisms leading to establishment of systemic disease after complete resection are mostly unknown. We therefore aimed at identifying molecular signatures of resected lung adenocarcinomas associated with the risk of an early relapse. The study comprised 89 patients with totally resected stage IA-IIIA lung adenocarcinomas. Patients suffering from an early relapse within two years after surgery were compared to patients without a relapse in two years. Patients were clinically and molecular pathologically characterized. Tumor tissues were immunohistochemically analyzed for the expression of Ki67, CD45, CD4, CD8, PD1, PD-L1, PD-L2 and CD34, by Nanostring nCounter PanCancer Immune Profiling Panel as well as a comprehensive methylome profiling using the Infinium MethylationEPIC BeadChip. We detected differential DNA methylation patterns as well as significantly differentially expressed genes associated with an early relapse after complete resection. Especially, CD1A was identified as a potential biomarker, whose reduced expression is associated with an early relapse. These findings might help to develop biomarkers improving risk assessment and patient selection for adjuvant therapy as well as establish novel targeted therapeutic strategies.
| S-EPMC8099905 | biostudies-literature
Project description:We identified a relapse-related molecular signature represented by 82 probes (RRS-82) through genome-wide expression profiling analysis of a training set of 60 patients. The robustness of RRS-82 in the selection of patients with a high probability of relapse was then validated with a completely blinded test set of 27 adenocarcinoma patients, showing a clear association of high risk RRS-82 with very poor patient prognosis regardless of disease stage. The discriminatory power of RRS-82 was further validated using an additional independent cohort of 30 Stage I patients who underwent surgery at a distinct period of time. Keywords: Disease state analysis
2009-06-23 | GSE13213 | GEO
Project description:Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer death worldwide, of which approximately 85% are non-small cell lung cancer (NSCLC). The overall survival (OS) of patients with advanced NSCLC was significantly prolonged with immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) axis. For early-stage lung cancer, the 5-year survival rate for patients ranges from 80% in stage IA to 41% in stage IIIA, and many cases relapse after surgical resection. Currently, multiple clinical trials have manifested the encouraging efficacy of neoadjuvant immunotherapy in stage I-IIIA resectable NSCLC. However, the effect of immunotherapy in ultra early-stage NSCLC patients with micro-invasive or even pre-invasive lesions remains unclear. In this study, we aimed to evaluate the activity and safety of sintilimab on high-risk ground glass opacity lesions in multiple primary lung cancer patients.
2024-05-01 | GSE260770 | GEO
Project description:This series studied the patterns of gene expression among different types of gastric tumors. Gastric tumors and adjacent non-tumor normal tissues were obtained from 50 gastric cancer patients of diverse stages (IA, IB, II, IIIA, IIIB, and IV), tumor types (intestinal, diffuse, or mixed), and degree of tumor differentiation (moderately or poorly differentiated). Keywords: Cancer patient samples
2006-06-01 | GSE3438 | GEO
Project description:Background Identification of patients at risk of tuberculosis relapse following treatment would revolutionize clinical trials of new drugs and regimens and facilitate clinical management. The study aim was to determine whether tuberculosis patients who subsequently suffer relapse have different immune responses to mycobacteria in vitro compared to patients who remain cured for two years post-treatment. Methods First episode pulmonary tuberculosis patients were recruited into a surrogate marker study in Cape Town, South Africa. Peripheral blood samples were collected at diagnosis and after two and four weeks of tuberculosis treatment. Diluted blood was cultured with live Mycobacterium tuberculosis for six days and cellular RNA was frozen. Gene expression in samples from ten patients who subsequently relapsed, confirmed by stain genotyping, was compared to those who remained cured using Affymetrix microarrays. Results At diagnosis, the expression of 668 genes was significantly different in samples from patients who subsequently relapsed compared to successfully cured patients, and these differences persisted for at least four weeks. Gene Ontology and biological pathways analyses revealed the most significant difference was up-regulation of genes involved in cytotoxic cell-mediated killing, such as perforin, granulysin and fas ligand. Results were confirmed by qRT-PCR in a wider patient cohort. Conclusions These data show that patients who will subsequently relapse exhibit altered immune responses at diagnosis, including excessively robust cytolytic responses to M. tuberculosis in vitro, compared to patients who will achieve durable cure. Together with microbiological and clinical indices, these differences could be exploited for patient stratification in drugs trials, or for host-directed therapy development. Venous blood samples were diluted in culture medium and stimulated with live M. tuberculosis for 6 days. Samples from 10 TB patients who subsequently relapsed and 10 patients whore remained disease-free for 2 years. Samples collected at TB diagnosis and after 2 weeks or 4 weeks of treatment of first TB episode.
2015-09-10 | E-GEOD-67589 | biostudies-arrayexpress
Project description:Wilms tumor (WT), the commonest renal tumor of the childhood, is originated from pluripotent metanephric blastemal cells resulting in tumors with triphasic histology, composed by blastemal, epithelial, and stromal cells. Histological subtype and tumor stage have long been recognized as important prognostic factors and used for the current therapeutic approach with blastema considered as the component with the highest clinical impact. Current clinical and molecular research is directed toward identifying prognostic factors for both purposes, definition of the minimal or intense required therapy for successful treatment of children with low or high risk of relapse, respectively. In this study, to identify molecular prognostic markers predictive of tumor relapse, samples from 26 advanced (Stage III or IV) blastemal WT, whose patients presented (13 samples) or did not present (13 samples) relapse, were interrogated by 4,608 human genes immobilized in a customized cDNA platform. This analysis revealed a set of 69 differentially expressed genes, where the nine top genes were evaluated by qRT-PCR in the initial WT samples. TSPAN3, NCOA6, CDO1, MPP2 and MCM2 were technically confirmed showing down-regulation in relapse WT. TSPAN3 and NCOA6 were validated in an independent sample group. Gene trios containing these two genes combined with one of the remaining three reported a reasonable capability of discriminating relapse and no-relapse WT. Negative protein expression of MCM2 and NCOA6 was observed in around 62% and 72% of 34 independent stage III and IV WT patients, respectively without association with relapse. However, a significant association between MCM2 negative staining and chemotherapy as first treatment was observed suggesting that MCM2 protein expression is implicated anyhow with chemotherapy treatment in WT. Twenty-six blastemal-enriched advanced stage (III or IV) WT samples from sporadic and favorable histology WT were received from Children Oncology Group (COG) and used were used for microarray experiments, from which 13 samples were from patients without relapse in 5 years of follow up. Tumors were taken from primary nephrectomy at the time of initial diagnosis. Blastemal histological component was isolated following protocol described in Maschietto et al. (2008). Only samples with >80% of blastemal cells were used. Total RNA was isolated using TRIzol (Sigma) according to manufacturer´s instructions. RNA quantity and integrity was assessed by spectrophotometry (Nanodrop) and microfluidics-based electrophoresis (Agilent 2100 Bioanalyzer, Agilent), respectively, selecting only RNA samples with OD around 2.0 and RIN>5.0. A two-round RNA amplification procedure (Gomes et al. 2003) was carried out for all samples. Labeled cDNA was generated in a reverse transcriptase reaction using 4 ug of amplified RNA (aRNA), random hexamer primer (Invitrogen Life Technologies, Carlsbad, CA), Alexa-3 or 5-labeled dCTP (Amersham, Biosciences) and IMPROM (PROMEGA) using oligo-dT7(24), following manufacture recommendations. Five µg of test and reference cDNA reverse color Alexa-labeled aRNA targets were competitively hybridized against the cDNA probes in a customized cDNA platform with 4,608 ORESTES representing human genes. Dye-swap was performed for each sample as control for dye bias and used as replicate. Pre-hybridization and hybridization were performed as described (Maschietto et al. 2008). A pool of RNAs obtained from 15 distinct human cell lines as was used as reference. Signal intensities capture and analysis were performed as described in Maschietto et al (2008).
2011-06-01 | E-GEOD-22696 | biostudies-arrayexpress
Project description:Here we characterize an association between disease progression and DNA methylation in Diffuse Large B cell Lymphoma (DLBCL). By profiling genome-wide DNA methylation at single base-pair resolution in thirteen DLBCL diagnosis-relapse sample pairs, we show DLBCL patients exhibit heterogeneous evolution of tumor methylomes during relapse. We identify differentially methylated regulatory elements and determine a relapse–associated methylation signature converging on key pathways such as transforming growth factor beta (TGF-beta) receptor activity. We also observe decreased intra-tumor methylation heterogeneity from diagnosis to relapsed tumor samples. Relapse-free patients display lower intra-tumor methylation heterogeneity at diagnosis compared to relapsed patients in an independent validation cohort. Furthermore, intra-tumor methylation heterogeneity is predictive of time to relapse. Therefore, we propose that epigenomic heterogeneity may support or drive the relapse phenotype and can be used to predict DLBCL relapse. Using ERRBS, we profiled genome-wide DNA methylation patterns of non-relapse DLBCL tumor samples at diagnosis, relaspe DLBCL patient samples at diagnosis and relaspe.
2015-04-14 | E-GEOD-66329 | biostudies-arrayexpress
Project description:Almost a quarter of pediatric patients with Acute Lymphoblastic Leukemia (ALL) suffer from relapses. The biological mechanisms underlying therapy response and development of relapses have remained unclear. In an attempt to better understand this phenomenon, we have analyzed 41 matched diagnosis relapse pairs of ALL patients using genomeâ??wide expression arrays (82 arrays) on purified leukemic cells. In roughly half of the patients very few differences between diagnosis and relapse samples were found (â??stable groupâ??), suggesting that mostly extra-leukemic factors (e.g., drug distribution, drug metabolism, compliance) contributed to the relapse. Therefore, we focused our further analysis on 20 samples with clear differences in gene expression (â??skewed groupâ??), reasoning that these would allow us to better study the biological mechanisms underlying relapsed ALL. After finding the differences between diagnosis and relapse pairs in this group, we identified four major gene clusters corresponding to several pathways associated with changes in cell cycle, DNA replication, recombination and repair, as well as B cell developmental genes. We also identified cancer genes commonly associated with colon carcinomas and ubiquitination to be upregulated in relapsed ALL. Thus, about half of relapses are due to selection or emergence of a clone with deregulated expression of a genes involved in pathways that regulate B cell signaling, development, cell cycle, cellular division and replication. The study contains 41 pairs of samples taken from patients at diagnosis and relapse (a total of 82 arrays).
2010-03-23 | E-GEOD-18497 | biostudies-arrayexpress
Project description:Although approximately 80% of adult patients with cytogenetically normal acute myeloid leukemia (CN-AML) achieve a complete remission (CR), over half of them relapse. Better identification of patients who are likely to relapse can help inform clinical decisions. We performed RNA sequencing on pretreatment samples from 268 adults with de novo CN-AML younger than 60 years who achieved a CR after induction treatment with standard “7+3” chemotherapy. After filtering for genes whose expressions were associated with gene mutations known to impact on outcome (i.e., CEBPA, NPM1, and FLT3-internal tandem duplication [FLT3-ITD]), we identified a 10-gene signature strongly predictive of patient relapse (area under the curve [AUC]=0.81). The signature consisted of seven coding genes: GAS6, PSD3, PLCB4, DEXI, JMY, NRP1, C10orf55, and three long non-coding RNAs. In multivariable analysis, the 10-gene signature was strongly associated with relapse (P<.001), after adjustment for the FLT3-ITD, CEBPA and NPM1 mutational status. Validation of the expression signature in an independent patient set from The Cancer Genome Atlas showed the signature’s strong predictive value with AUC=0.78. Implementation of the 10-gene signature into clinical prognostic stratification could be useful for identifying patients likely to relapse.
2021-03-16 | GSE165430 | GEO