Immunological modifications following chemotherapy are associated with delayed recurrence of ovarian cancer
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PROVIDER: PRJNA943229 | ENA |
REPOSITORIES: ENA
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Project description:IntroductionOvarian cancer recurs in most High Grade Serous Ovarian Cancer (HGSOC) patients, including initial responders, after standard of care. To improve patient survival, we need to identify and understand the factors contributing to early or late recurrence and therapeutically target these mechanisms. We hypothesized that in HGSOC, the response to chemotherapy is associated with a specific gene expression signature determined by the tumor microenvironment. In this study, we sought to determine the differences in gene expression and the tumor immune microenvironment between patients who show early recurrence (within 6 months) compared to those who show late recurrence following chemotherapy.MethodsPaired tumor samples were obtained before and after Carboplatin and Taxol chemotherapy from 24 patients with HGSOC. Bioinformatic transcriptomic analysis was performed on the tumor samples to determine the gene expression signature associated with differences in recurrence pattern. Gene Ontology and Pathway analysis was performed using AdvaitaBio's iPathwayGuide software. Tumor immune cell fractions were imputed using CIBERSORTx. Results were compared between late recurrence and early recurrence patients, and between paired pre-chemotherapy and post-chemotherapy samples.ResultsThere was no statistically significant difference between early recurrence or late recurrence ovarian tumors pre-chemotherapy. However, chemotherapy induced significant immunological changes in tumors from late recurrence patients but had no impact on tumors from early recurrence patients. The key immunological change induced by chemotherapy in late recurrence patients was the reversal of pro-tumor immune signature.DiscussionWe report for the first time, the association between immunological modifications in response to chemotherapy and the time of recurrence. Our findings provide novel opportunities to ultimately improve ovarian cancer patient survival.
| S-EPMC10331425 | biostudies-literature
Project description:This study was conducted to determine why some high grade serous ovarian cancer (HGSOC) patients recur earlier than others following treatment
2023-06-21 | GSE227100 | GEO
Project description:To find metastatic recurrence biomarkers of triple negative breast cancer (TNBC) treated by neoadjuvant chemotherapy and anti-EGFR antibodies (NAT), we evaluated tumor genomic, transcriptomic and immune features, using MSK-IMPACT assay, gene arrays, Nanostring technology and TIL assessment on H&E. Six patients experienced a rapid fatal recurrence (RR) and other 6 had later non-fatal recurrences (LR). Before NAT, RR had low expression of 6 MHC class I and 13 MHC class II genes but were enriched in upregulated genes involved in the cell cycle-related pathways. Their TIL number before NAT in RR was very low (<5%) and did not increase after treatment. In post-NAT residual tumors, RR cases showed high expression of SOX2 and CXCR4. Our results indicate that high expression of cell cycle genes, combined with cold immunological phenotype, may predict strong TNBC resistance to NAT and rapid progression after it. This biomarker combination is worth validation in larger studies.
2021-07-26 | GSE180717 | GEO
Project description:To find metastatic recurrence biomarkers of triple negative breast cancer (TNBC) treated by neoadjuvant chemotherapy and anti-EGFR antibodies (NAT), we evaluated tumor genomic, transcriptomic and immune features, using MSK-IMPACT assay, gene arrays, Nanostring technology and TIL assessment on H&E. Six patients experienced a rapid fatal recurrence (RR) and other 6 had later non-fatal recurrences (LR). Before NAT, RR had low expression of 6 MHC class I and 13 MHC class II genes but were enriched in upregulated genes involved in the cell cycle-related pathways. Their TIL number before NAT in RR was very low (<5%) and did not increase after treatment. In post-NAT residual tumors, RR cases showed high expression of SOX2 and CXCR4. Our results indicate that high expression of cell cycle genes, combined with cold immunological phenotype, may predict strong TNBC resistance to NAT and rapid progression after it. This biomarker combination is worth validation in larger studies.
2021-07-28 | GSE180775 | GEO
Project description:Gene expression changes in colon cancer spheroids induced by chemotherapy.
2018-08-01 | GSE97781 | GEO
Project description:We lack tools to risk-stratify triple-negative breast cancer (TNBC). Our goal was to develop molecular tools to predict disease recurrence. Methylation array analysis was performed on 110 samples treated by locoregional therapy obtained from Institutional cohorts. Discovered marker sets were then tested by Kaplan Meier analyses in a prospectively collected TNBC cohort of 49 samples from the no chemotherapy arms of IBCSG trials VIII and IX, and by logistic regression in a chemotherapy-treated cohort of 121 TNBCs from combined IBCSG trials and Institutional repositories. High methylation was associated with shorter recurrence-free interval in the no chemotherapy arm of the IBCSG studies, as well as in the chemotherapy-treated patients within the combined Institutional and IBCSG chemotherapy cohorts (100 marker panel, P=0.002; 30 marker panel, P=0.05). Chromosome 19 sites were enriched among these loci. In conclusion, our hypermethylation signatures identify increased recurrence risk independent of whether patients receive chemotherapy.
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Project description:Quiescent human glioblastoma cancer stem cells mediate tumor initiation, expansion, and recurrence following chemotherapy
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Project description:This series contains the gene expression data from urothelial bladder cancer samples from Swedish patients that were used to analyze metastatic sites. Included patients have a recurrence or distant metastasis before or after treatment with chemotherapy. Patients with only lymph-node metastases are not included. A previous series (GSE169455) contains data from all patients that recieved two or more cycles of neoadjuvant chemotherapy with curative intent. Patients in that series that developed distant recurrence are re-analyzed here. A few samples from a previous cystectomy series (GSE83586) are also included as re-analysis. In addition, the current series contains data from patients treated with palliative first-line chemotherapy, curative adjuvant chemotherapy, or < 2 cycles of neoadjuvant chemotherapy. Raw data should be adjusted in data processing for batch variables: Labeling batch and Labeling kit.
2023-08-24 | GSE222073 | GEO
Project description:Cancer recurrence and chemoresistance are the leading causes of death in high-grade serous ovarian cancer (HGSOC) patients. However, the unique role of the immune environment in tumor progression for relapsed chemo-resistant patients remains elusive. In single-cell resolution, we characterized a comprehensive multi-dimensional cellular and immunological atlas from tumor, ascites, and peripheral blood of a chemo-resistant patient at different stages of treatment. Our results highlight a role in recurrence and chemoresistance of the immunosuppressive microenvironment in ascites, including MDSC-like myeloid and hypo-metabolic γδT cells, and of peripheral CD8+ effector T cells with chemotherapy-induced senescent/exhaustive. Importantly, paired TCR/BCR sequencing demonstrated relative conservation of TCR clonal expansion in hyper-expanded CD8+ T cells and extensive BCR clonal expansion without usage bias of V(D)J genes after chemotherapy. Thus, our study suggests strategies for ameliorating chemotherapy-induced immune impairment to improve the clinical outcome of HGSOC.
2022-09-15 | GSE213243 | GEO
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