Expression of keratin-1 predicts recurrence and treatment response in advanced laryngeal cancer: a potential therapeutic target
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE293443 | GEO | 2025/04/01
REPOSITORIES: GEO
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Project description:T cell senescence is a dysfunctional state distinct from exhaustion, yet the mechanism driving CD8+ T cell senescence directly in tumor microenvironment and its impact on cancer prognosis remain elusive. Here, by using single cell RNA sequencing of human cervical cancer tissues, we found that concurrent chemoradiotherapy (CCRT) specifically promoted CD8+ T cell senescence, which is driven by a subpopulation of ACKR2+ CCRT-resistance tumor cells. Mechanistically, in response to CCRT treatment, ACKR2 was directly induced and could also be upregulated through its ligands CC chemokines that produced by activated myeloid and T cells. Subsequently, these ACKR2+ tumor cell subpopulation also produced TGFβ to drive CD8+ T cell senescence, thereby compromising antitumor immunity. Moreover, retrospective analysis showed that ACKR2 level and CD8+ T cell senescence was greatly enhanced in cervical cancer patients who recurred after CCRT, thereby predicting poor prognosis in these patients. Overall, we identified a subpopulation of CCRT-resistant ACKR2+ tumor cells in driving CD8+ T cell senescence and thus tumor recurrence, which may represent a critical mechanism in mediating CCRT resistance, and highlighted the therapeutic potential of targeting ACKR2 or CD8+ T cell senescence in the treatment of CCRT-resistant cancer patients.
2024-06-07 | GSE236738 | GEO
Project description:Background/Aims: Recurrence-free survival (RFS) following curative resection of hepatocellular carcinoma (HCC) in subjects with hepatitis C virus (HCV) infection is highly variable. Traditional clinico-pathological endpoints are recognized as weak predictors of RFS. It has been suggested that gene expression profiling of HCC and nontumoral liver tissue may improve prediction of RFS, aid in understanding of the underlying liver disease, and guide individualized therapy. The goal of this study was to create a gene expression predictor of HCC recurrence in subjects with HCV. Methods: Frozen samples of the tumors and nontumoral liver were obtained from 47 subjects with HCV-associated HCC. Additional nontumoral liver samples were obtained from HCV-free subjects with metastatic liver tumors. Gene expression profiling data was used to determine the molecular signature of HCV-associated HCC and to develop a predictor of RFS. Results: The molecular profile of the HCV-associated HCC confirmed central roles for MYC and TGF-beta1 in liver tumor development. Gene expression in tumors was found to have poor predictive power with regards to RFS, but analysis of nontumoral tissues yielded a strong predictor for RFS in late-recurring (>1 year) subjects. Importantly, nontumoral tissue-derived gene expression predictor of RFS was highly significant in both univariable and multivariable Cox proportional hazard model analyses. Conclusions: Microarray analysis of the nontumoral tissues from subjects with HCV-associated HCC delivers novel molecular signatures of RFS, especially among the late-recurrence subjects. The gene expression signature of the predictor gives important insights into the pathobiology of HCC recurrence and used in design of the individualized therapy. 43 tumor (JT) and 44 non-tumor (JNT) liver tissues surgically resected from patients with HCV-associated hepatocellular carcinoma; 8 non-tumor liver tissues (control samples, JC) surgically resected from HCV- or HBV-free patients with metastatic liver tumor. Inter-batch normalization was carried out using Distance Weighted Discrimination procedure. The supplementary file 'GSE17856_Readme.txt' contains a description of the replicates used for normalization. The 'GSE17856_US14702406_2514850*' files are the raw data files for the replicates.
2010-04-14 | E-GEOD-17856 | biostudies-arrayexpress
Project description:Despite surgical treatment of stage I non-small cell lung cancer (NSCLC), one third of patients will eventually have a recurrence. Robust prognostic markers are required to better manage therapy options. MicroRNAs play important roles in human cancers. The purpose of this study is to identify miRNA expression profiles that would better predict prognosis. Small RNAs extracted from formalin-fixed and paraffin-embedded (FFPE) tumor tissues of 357 stage I NSCLC patients were profiled on the human MicroRNA expression profiling V2 panel (Illumina). The expression differences between cancer subtypes were compared by t tests. The association of miRNA expression profile with recurrence free survival (RFS) was assessed using partial Cox regression models. Two miRNA signatures that are highly predictive of RFS were identified. The first contained 32 miRNAs derived from 357 stage I NSCLC patients independent of cancer subtype; while the second containing 27 miRNAs was adenocarcinoma specific. Both of them were validated using FFPE and/or fresh frozen tissues in independent data set with 170 stage I patients. This has important prognostic or therapeutic implications for the management of patients. The identified miRNAs hold great potential as targets for histology-specific treatment or prevention and treatment of recurrent disease. Small RNAs extracted from formalin-fixed and paraffin-embedded (FFPE) tumor tissues of 357 stage I NSCLC patients were profiled on the human MicroRNA expression profiling V2 panel (Illumina).
2012-03-26 | E-GEOD-29135 | biostudies-arrayexpress
Project description:Background/Aims: Recurrence-free survival (RFS) following curative resection of hepatocellular carcinoma (HCC) in subjects with hepatitis C virus (HCV) infection is highly variable. Traditional clinico-pathological endpoints are recognized as weak predictors of RFS. It has been suggested that gene expression profiling of HCC and nontumoral liver tissue may improve prediction of RFS, aid in understanding of the underlying liver disease, and guide individualized therapy. The goal of this study was to create a gene expression predictor of HCC recurrence in subjects with HCV. Methods: Frozen samples of the tumors and nontumoral liver were obtained from 47 subjects with HCV-associated HCC. Additional nontumoral liver samples were obtained from HCV-free subjects with metastatic liver tumors. Gene expression profiling data was used to determine the molecular signature of HCV-associated HCC and to develop a predictor of RFS. Results: The molecular profile of the HCV-associated HCC confirmed central roles for MYC and TGF-beta1 in liver tumor development. Gene expression in tumors was found to have poor predictive power with regards to RFS, but analysis of nontumoral tissues yielded a strong predictor for RFS in late-recurring (>1 year) subjects. Importantly, nontumoral tissue-derived gene expression predictor of RFS was highly significant in both univariable and multivariable Cox proportional hazard model analyses. Conclusions: Microarray analysis of the nontumoral tissues from subjects with HCV-associated HCC delivers novel molecular signatures of RFS, especially among the late-recurrence subjects. The gene expression signature of the predictor gives important insights into the pathobiology of HCC recurrence and used in design of the individualized therapy.
2010-04-14 | GSE17856 | GEO
Project description:Keratin 1 (KRT1) and its heterodimer partner keratin 10 (KRT10) constitute the intermediate filament cytoskeleton of suprabasal skin keratinocytes. They participate in formation of the epidermal barrier, which protects against dehydration and inflammation. Mutations in KRT1 cause keratinopathic ichthyosis with erythema, recurrent inflammation, and barrier defects. Here, we show that genetic deletion of Krt1 in mice causes a defective inside-out epidermal barrier, pre- and postnatal increases in Mrp8/Mrp14, interleukin (IL) 18, IL-33, and thymic stromal lymphopoietin (TSLP) in skin extracts, and systemic release of IL-18 into newborn serum. Perinatal lethality was partially rescued by treatment with glucocorticoids to promote barrier repair or with IL- 18-blocking antibodies in utero. In human keratinocytes, IL-18 release was cellautonomous and caspase-1-dependent, indicating KRT1-dependent inflammasome activation. Our data reveal a novl function of KRT1 in controlling inflammasome activity and stimulating barrier formation, thereby integrating the keratin cytoskeleton into the epidermal immune response. In view of their widespread expression, keratins merit investigation of their functions in inflammatory conditions, including asthma and inflammatory bowel disorders. Total RNA was obtained from epidermis or full-thickness skin of Krt1+/+ and Krt1-/- mice (C57BL/6 background) at P0 (newborn).
2012-12-01 | E-GEOD-32951 | biostudies-arrayexpress
Project description:In this study, esophageal squamous cell carcinoma (ESCC) patients’ endoscopic biopsy tumor tissues obtained before their concomitant chemo-radiation therapy (CCRT) were used to analyze the transcriptomes by using the RNA-sequencing approach. According to retrospective study of patients’ responses to CCRT, the treatment-naive specimen can be divided into two groups (16 good CCRT response and 12 poor CCRT response). This systematic profiling uncovered a gene set that is differentially expressed between the two patient groups.
2022-11-02 | GSE199630 | GEO
Project description:Postoperative recurrence is the main cause of poor prognosis in early stage lung adenocarcinoma (LUAD). Factors that can predict recurrence risk are critically needed.we designed a screening procedure based on gene profile data.The differentially expressed genes (DEGs) between patients with recurrence-free survival (RFS)<1 year and RFS>3 years were found.Cox proportional hazards model, IHC and Kaplan-Meier survival analysis were preformed to validate these biomarkers in TCGA and Daping validation sets.
2018-10-27 | GSE121841 | GEO
Project description:Despite surgical treatment of stage I non-small cell lung cancer (NSCLC), one third of patients will eventually have a recurrence. Robust prognostic markers are required to better manage therapy options. MicroRNAs play important roles in human cancers. The purpose of this study is to identify miRNA expression profiles that would better predict prognosis. Small RNAs extracted from formalin-fixed and paraffin-embedded (FFPE) tumor tissues of 357 stage I NSCLC patients were profiled on the human MicroRNA expression profiling V2 panel (Illumina). The expression differences between cancer subtypes were compared by t tests. The association of miRNA expression profile with recurrence free survival (RFS) was assessed using partial Cox regression models. Two miRNA signatures that are highly predictive of RFS were identified. The first contained 32 miRNAs derived from 357 stage I NSCLC patients independent of cancer subtype; while the second containing 27 miRNAs was adenocarcinoma specific. Both of them were validated using FFPE and/or fresh frozen tissues in independent data set with 170 stage I patients. This has important prognostic or therapeutic implications for the management of patients. The identified miRNAs hold great potential as targets for histology-specific treatment or prevention and treatment of recurrent disease.
2012-03-27 | GSE29135 | GEO
Project description:BACKGROUND & AIMS: Sorafenib is the standard systemic therapy for advanced hepatocellular carcinoma (HCC). In early-stage HCC, survival benefits of resection/local ablation are compromised by high recurrence rates (70% at 5-years). In this setting, the phase-3 STORM-trial did not achieve its primary end-point of improving recurrence-free-survival (RFS) comparing sorafenib to placebo as adjuvant treatment. Herein we present results of the biomarker companion study BIOSTORM in which we define predictors of recurrence prevention with sorafenib and prognostic factors with B-level of evidence. METHODS: Tumor tissue from 188 patients randomized to receive sorafenib (83) or placebo (105) in the STORM trial was collected. Analyses included gene-expression profiling, targeted exome sequencing (18 known onco-drivers), immunohistochemistry (pERK, pVEGFR2, Ki67), FISH (VEGFA) and immunome. A gene signature capturing improved RFS in sorafenib-treated patients was generated. All 70 RFS events were recurrences, thus time-to-recurrence equaled RFS. Predictive and prognostic value was assessed using Cox regression models and interaction test. RESULTS: BIOSTORM recapitulates clinical and pathological characteristics of STORM patients. None of the biomarkers tested that are known to be related to angiogenesis and proliferation, or previously proposed gene-signatures, or mutations predicted sorafenib benefit. A newly generated 146-gene signature identifying 30% of patients captured benefit to sorafenib in terms of RFS (p-of-interaction=0.04). These sorafenib responders were significantly enriched in CD4+ T, B, and cytolytic Natural Killer cells, and showed absence of activated macrophages and other components of adaptive immunity. Hepatocytic pERK (HR=2.41; p=0.012) and microvascular invasion (HR=2.09; p=0.017) were independent prognostic factors. CONCLUSIONS: In BIOSTORM, hepatocytic pERK and microvascular invasion predicted poor RFS. No mutation, gene amplification or previously proposed gene-signatures predicted sorafenib benefit. A newly generated multi-gene signature associated with improved RFS on sorafenib warrants further validation. KEYWORDS: sorafenib; tyrosine-kinase inhibitor; trial enrichment; stratification.
2018-08-21 | GSE109211 | GEO
Project description:In this study, we aimed to explore the role of miR-145, which is downregulated in LSCC, on cancer stem cell potency of laryngeal cancer cells. Using microRNA expression profiling and experimental follow-up studies, we demonstrated the regulatory role of miR-145 in stem cell characteristics of Hep-2 cells. Based on these results, we propose that mir-145 might carry crucial roles in LSCC tumorigenesis, prognosis, metastasis, chemoresistance and recurrence through regulating stem cell properties of tumor cells. LSCC tissue samples and normal tissues were profiled for microRNA expression; cancer tissue profiles were compared with normal tissue profiles.
2015-11-10 | E-GEOD-70289 | biostudies-arrayexpress