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Identification of differentially expressed miRNAs in PD vs. nonPD in cancer samples

ABSTRACT: Lack of a standard method for stratifying advanced-stage NSCLC patients receiving platinum combination therapy often results in a number of patients that do not derive benefit yet are still exposed to treatment toxicity. We hypothesized that miRNAs in pre-treatment serum and/or plasma could be used to differentiate non-small cell lung cancer (NSCLC) patients who would have disease progression to first-line carboplatin and gemcitabine chemotherapy at first response assessment. miRNA profiling of mature and precursor miRNAs was performed on total RNA isolated from the pre-treatment serum and plasma of 24 NSCLC patients. Single validated candidates or combinations thereof were selected based on specificity and sensitivity to segregate patients with disease progression at first radiologic response (PD) vs. those without progressed disease (nonPD). Two precursor miRNA were significantly over-expressed in serum (but not plasma) of PD patients: pre-miR-518b and pre-miR-598. Serum miRNAs may serve as a screening tool in predicting chemoresistance to platinum-based combination chemotherapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE25019 | GEO | 2012/12/01

SECONDARY ACCESSION(S): PRJNA134389

REPOSITORIES: GEO

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Identification of differentially expressed miRNAs in PD vs. nonPD in cancer samples

Project description:Lack of a standard method for stratifying advanced-stage NSCLC patients receiving platinum combination therapy often results in a number of patients that do not derive benefit yet are still exposed to treatment toxicity. We hypothesized that miRNAs in pre-treatment serum and/or plasma could be used to differentiate non-small cell lung cancer (NSCLC) patients who would have disease progression to first-line carboplatin and gemcitabine chemotherapy at first response assessment. miRNA profiling of mature and precursor miRNAs was performed on total RNA isolated from the pre-treatment serum and plasma of 24 NSCLC patients. Single validated candidates or combinations thereof were selected based on specificity and sensitivity to segregate patients with disease progression at first radiologic response (PD) vs. those without progressed disease (nonPD). Two precursor miRNA were significantly over-expressed in serum (but not plasma) of PD patients: pre-miR-518b and pre-miR-598. Serum miRNAs may serve as a screening tool in predicting chemoresistance to platinum-based combination chemotherapy. miRNA microarray was performed on RNA extracted from matched human serum or plasma obtained from NSCLC patients

2012-12-01 | E-GEOD-25019 | biostudies-arrayexpress

Chemotherapy negatively impacts the tumor immune microenvironment in NSCLC: An analysis of pre- and post-treatment biopsies in the multi-center SAKK19/09 study

Project description:Background: Over the past few years, immune checkpoint inhibitors have changed the therapeutic landscape of non-small-cell lung cancer (NSCLC). Response to immune checkpoint inhibitors correlates with a pre-existing anti-tumoral immune response. Checkpoint inhibitors have been introduced as second line therapy and are only very recently used as monotherapy or in combination with chemotherapy as first line treatment of NSCLC. However, the effect of conventional first line platinum-based chemotherapy on the immune infiltrate in the tumor is largely unknown. Methods: We measured the gene expression of a custom set of 201 cancer- and immune-related genes in 100 NSCLC tumor biopsies collected before chemotherapy and 33 re-biopsies after platinum-based chemotherapy at the time point of progression. For 29 patients matched pre- and post-chemotherapy samples could be evaluated. Results: We identified a cluster of 47 co-expressed immune genes, including PDCD1 (PD1) and CD274 (PD-L1), along with three other co-expression clusters. Chemotherapy decreased the average gene expression of the immune cluster while no effect was observed on the other three cluster. Within this immune cluster, CTLA4, LAG3, TNFRSF18, CD80 and FOXP3 were found to be significantly decreased in patient-matched samples after chemotherapy. Conclusion: Our results suggest that conventional platinum-based chemotherapy negatively impacts the immune microenvironment at the time point of secondary progression.

2020-07-14 | GSE154286 | GEO

The expression profiles of exosomal miRNAs associated with response to anti-PD-1/PD-L1 monotherapy in advanced NSCLC patients.

Project description:Exosomal miRNAs involved in response to anti-PD-1/PD-L1 monotherapy in advanced NSCLC patients were successfully identified through the microoarray analysis.

2023-01-12 | GSE189045 | GEO

microRNA microarray on a cohort study of platinum-sensitive versus platinum-resistant NSCLC patients

Project description:To identify microRNAs that regulate therapeutic resistance, we conducted a high-throughput miRNA microarray on a cohort study of primary NSCLC (non-small cell lung cancer) tissues and adjacent normal tissues. We found some microRNAs related to therapeutic resistance and poor prognosis. In this study, the patients who were diagnosed with resected NSCLC (adenocarcinoma or squamous cell carcinoma) were enrolled. All tumors were reviewed by pathologists and were pathologically diagnosed according to the World Health Organisation Classification of Tumors. Twenty-nine patients who received four or more courses of first-line platinum-based chemotherapy after postoperative recurrence were divided into two groups (responder (n=17) and non-responder group (n=12)). As identified by ANOVA analysis and quantitative RT-PCR (qRT-PCR) of 4 groups, some miRNAs exhibited significant expression changes.

2015-04-15 | E-GEOD-56036 | biostudies-arrayexpress

Soluble immune-checkpoint factors as a complementary biomarker for PD-1 blockade reflect exhaustion of antitumor immunity

Project description:BACKGROUND. Precise stratification of patients with non–small cell lung cancer (NSCLC) is needed for appropriate application of PD-1/PD-L1 blockade therapy. METHODS. We measured soluble (s) forms of the PD-L1, PD-1, and CTLA-4 in plasma of patients with advanced NSCLC before PD-1/PD-L1 blockade. Prospective biomarker finding trial (cohort A), 50 patients with pretreated NSCLC received nivolumab. In cohort B to E, retrospective observational study, soluble immune checkpoint molecules were evaluated for patients with advanced NSCLC treated with any PD-1/PD-L1 blockade (cohort B and C), cytotoxic chemotherapy (D) or targeted therapy (E). Blood samples were obtained from all patients and soluble immune checkpoint molecules were evaluated using a highly sensitive chemiluminescence-based assay. RESULTS. Nonresponsiveness to PD-1/PD-L1 blockade therapy was associated with higher concentrations of these soluble immune factors among patients with immune-reactive (hot) tumors. Such correlation was not observed in patients treated with cytotoxic chemotherapy or targeted therapies. Integrative analysis of tumor size, PD-L1 expression in tumor tissue (tPD-L1), and gene expression in tumor tissue and peripheral CD8+ T cells revealed that high concentrations of the three soluble immune factors were associated with hyper or terminal exhaustion of antitumor immunity. The combination of sPD-L1 and sCTLA-4 efficiently discriminated responsiveness among patients with immune-reactive tumors. CONCLUSION. Combinations of soluble immune factors might be able to identify patients unlikely to respond to PD-1/PD-L1 blockade as a result of terminal exhaustion of antitumor immunity. Our data suggest such a combination might provide a biomarker complementary to tPD-L1 for NSCLC patients.

2024-03-30 | GSE242860 | GEO

Gene expression-signatures for non-small cell lung cancer patients with different EGFR muational status.

Project description:To identify a plasma miRNA panel that could help to separate NSCLC patients with EGFR sensitive mutations and wild-type EGFR, plasma samples of 3 EGFR19DEL, 3 EGFRp.L858R, and 3 EGFRWT patients with NSCLC and 4 HCs were selected for Agilent miRNA microarray analysis to detect differences in the expression levels of circulating miRNAs (n = 2,568) between the above cohorts.

2017-01-10 | GSE93300 | GEO

Gene expression-signatures for non-small cell lung cancer patients with different ALK mutational status.

Project description:To identify a plasma microRNA panel that could help to distinguish ALK positive with ALK negative NSCLC patients, plasma samples of 3 ALK-positive, 3 ALK-negative NSCLC, and 3 Healthy Subjects were selected for Agilent miRNA microarray analysis to detect differences in the expression levels of circulating miRNAs (n = 2568) between the above cohorts.

2017-02-07 | GSE94536 | GEO

Next generation sequencing identifies differentially expressed tRNA-derived fragments (tRF) in the plasma of patients with non-small cell lung cancer (NSCLC)

Project description:We report the application of small RNA sequencing for high-throughput profiling of circulating tRF in the pre- and post-operation plasma from patients with NSCLC

2022-05-25 | GSE185546 | GEO

KIR Polymorphism is Associated with Primary Resistance to PD-1 Blockade in Lung Cancer

Project description:Adaptive immune escape of tumor cells by upregulation of ligands for programmed death 1 (PD-1) has been identified as an important and targetable pathway in many cancer types. Many clinical trials have demonstrated that targeting PD-1 or its ligand PD-L1 with immune checkpoint inhibitors (ICI) can restore anti-tumor immunity and induce durable remission. In patients with non-small cell lung cancer (NSCLC), several trials have demonstrated a survival benefit with ICI in patients with metastatic and locally advanced NSCLC.Yet, most patients have primary resistance to PD-1 or PD-L1 blockade during treatment: approximately 20% of unselected patients with NSCLC achieve a partial response while 40-50% have progressive disease as best response. Understanding mechanisms of primary resistance to PD-(L)1 blockade is important in the search for potentially targetable pathways and may ultimately allow discrimination between patients that benefit from PD-(L)1 blockade and those requiring combination or other approaches. We collected PBMCs and serum samples from 35 patients with NSCLC before and during PD-1 blockade treatment with nivolumab. We analyzed differentially expressed genes in CD8+ T cells from the peripheral blood of 5 patients with partial response and 5 patients with primary progressive disease to identify mechanisms of resistance to PD-1 therapy. Cells were collected from samples taken before and after 4 weeks of treatment.

2021-03-01 | GSE111414 | GEO

Identification of a plasma four-microRNA panel as a potential noninvasive biomarker for osteosarcoma

Project description:TaqMan low density array (TLDA) was carried out to screen of the profiles of circulating miRNAs in pooled plasma samples from healthy controls and pre-operative osteosarcoma patients. The expression changes of circulating miRNAs in osteosarcoma patients were identified. To select candidate plasma miRNAs for osteosarcoma detection and monitoring, we employed TLDA technique to screen expression levels of 739 miRNAs in pooled plasma samples from healthy controls and pre-operative osteosarcoma patients (each pooled from 10 individuals).

2015-01-13 | E-GEOD-64915 | biostudies-arrayexpress

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