Gene expression signatures for predicting prognosis of squamous cell lung carcinomas
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE4573 | GEO | 2006/03/30
SECONDARY ACCESSION(S): PRJNA94409
REPOSITORIES: GEO
Similar Datasets
Project description:Gene signatures were derived to separate high risk patients from low risk ones. Experiment Overall Design: 130 samples from 129 patients
2007-11-01 | E-GEOD-4573 | biostudies-arrayexpress
Project description:BackgroundCopy number alterations are common genetic lesions in cancer. In squamous non-small cell lung carcinomas, the most common copy-number-altered loci are at chromosomes 3q26-27 and 8p11.23. The genes that may be drivers in squamous lung cancers with 8p11.23 amplifications are unclear.MethodsData pertaining to copy number alterations, mRNA expression and protein expression of genes located in the 8p11.23 amplified region were extracted from various sources including The Cancer Genome Atlas, the Human Protein Atlas and the Kaplan Meier Plotter. Genomic data were analyzed using the cBioportal platform. Survival analysis of cases with amplifications compared to nonamplified cases was performed using the Kaplan Meier Plotter platform.ResultsThe 8p11.23 locus is amplified in 11.5% to 17.7% of squamous lung carcinomas. The most frequently amplified genes include NSD3, FGFR1 and LETM2. Only some of the amplified genes present concomitant overexpression at the mRNA level. These include NSD3, PLPP5, DDHD2, LSM1 and ASH2L, while other genes display lower levels of correlation, and still, some genes in the locus show no mRNA overexpression compared with copy-neutral samples. The protein products of most locus genes are expressed in squamous lung cancers. No significant difference in overall survival in 8p11.23-amplified squamous cell lung cancers versus nonamplified cancers is observed. In addition, there is no adverse effect of mRNA overexpression for relapse-free survival of any of the amplified genes.ConclusionSeveral genes that are part of the commonly amplified locus 8p11.23 in squamous lung carcinomas are putative oncogenic candidates. A subset of genes of the centromeric part of the locus, which is amplified more commonly than the telomeric part, show high concomitant mRNA expression.
| S-EPMC10002535 | biostudies-literature
Project description:Protein Co-expression Network-based Profiles Revealed from Laser-microdissected Cancerous Cells of Lung Squamous-Cell Carcinomas
2021-07-19 | PXD027381 | JPOST Repository
Project description:The microbiome is fundamentally one of the most unique organs in the human body. Dysbiosis can result in critical inflammatory responses and result in pathogenesis contributing to neoplastic events. We used a pan-pathogen array technology (PathoChip) coupled with next-generation sequencing to establish microbial signatures unique to human oral and oropharyngeal squamous cell carcinomas (OCSCC/OPSCC). Signatures for DNA and RNA viruses including oncogenic viruses, gram positive and negative bacteria, fungi and parasites were detected. Cluster and topological analyses identified 2 distinct groups of microbial signatures related to OCSCCs/OPSCCs. Results were validated by probe capture next generation sequencing; the data from which also provided a comprehensive map of integration sites and chromosomal hotspots for micro-organism genomic insertions. Identification of these microbial signatures and their integration sites may provide biomarkers for OCSCC/OPSCC diagnosis and prognosis as well as novel avenues for study of their potential role in OCSCCs/OPSCCs.
| S-EPMC5481414 | biostudies-literature
Project description:Growing evidence indicates that immune-related biomarkers play an important role in tumor processes. This study investigates immune-related gene expression and its prognostic value in lung squamous cell carcinoma (LUSC). A cohort of 493 samples of patients with LUSC was collected and analyzed from data generated by the TCGA Research Network and ImmPort database. The R coxph package was employed to mine significant immune-related genes using univariate analysis. Lasso and stepwise regression analyses were used to construct the LUSC prognosis prediction model, and clusterProfiler was used for gene functional annotation and enrichment analysis. The Kaplan-Meier analysis and ROC were used to evaluate the model efficiency in predicting and classifying LUSC case prognoses. We identified 14 immune-related genes to incorporate into our prognosis model. The patients were divided into two subgroups (Risk-H and Risk-L) according to their risk score values. Compared to Risk-L patients, Risk-H patients showed significantly improved overall survival (OS) in both training and testing sets. Functional annotation indicated that the 14 identified genes were mainly enriched in several immune-related pathways. Our results also revealed that a risk score value was correlated with various signaling pathways, such as the JAK-STA signaling pathway. Establishment of a nomogram for clinical application demonstrated that our immune-related model exhibited good predictive prognostic performance. Our predictive prognosis model based on immune signatures has potential clinical implications for assessing the overall survival and precise treatment for patients with LUSC.
| S-EPMC7338973 | biostudies-literature
Project description:The role of human papillomavirus (HPV) in anal squamous cell carcinoma (ASCC) carcinogenesis has been clearly established, involving the expression of viral oncoproteins and optional viral DNA integration into the host genome. In this article, we describe the various mechanisms and sites of HPV DNA insertion and assess their prognostic and predictive value in a large series of patients with HPV-positive ASCC with long-term follow-up. We retrospectively analyzed 96 tumor samples from 93 HPV-positive ASCC patients using the Capture-HPV method followed by Next-Generation Sequencing, allowing determination of HPV genotype and identification of the mechanisms and sites of viral genome integration. We identified five different mechanistic signatures of HPV insertions. The distribution of HPV signatures differed from that previously described in HPV-positive cervical carcinoma (p < 0.001). In ASCC samples, the HPV genome more frequently remained in episomal form (45.2%). The most common signature of HPV insertion was MJ-SC (26.9%), i.e., HPV-chromosomal junctions scattered at different loci. Functionally, HPV integration signatures were not associated with survival or response to treatment, but were associated with viral load (p = 0.022) and PIK3CA mutation (p = 0.0069). High viral load was associated with longer survival in both univariate (p = 0.044) and multivariate (p = 0.011) analyses. Finally, HPV integration occurred on most human chromosomes, but intragenic integration into the NFIX gene was recurrently observed (n = 4/51 tumors). Overall, the distribution of mechanistic signatures of HPV insertions in ASCC was different from that observed in cervical carcinoma and was associated with viral load and PIK3CA mutation. We confirmed recurrent targeting of NFIX by HPV integration, suggesting a role for this gene in ASCC carcinogenesis.
| S-EPMC6966520 | biostudies-literature
Project description:Abstract: Immunotherapy has emerged as a crucial treatment approach for lung adenocarcinoma (LUAD), yet a notable percentage of patients do not exhibit the anticipated prognosis and therapeutic response. In this study, we embarked on a comprehensive analysis of immune infiltration-related genes in LUAD by integrating transcriptome sequencing data and TCGA dataset. And an immune risk prognosis model was developed, which accurately forecasts the prognosis and predicts the immunotherapy efficacy in LUAD. Patients with LUAD were categorized into high-risk and low-risk groups based on the model's risk value. The high-risk group exhibited a poorer prognosis, higher tumor mutation burden (TMB), greater genomic heterogeneity and lower immune scores. In contrast, the low-risk group manifested characteristics conducive to immunotherapy, including a more favorable prognosis, heightened sensitivity to immunotherapy and reduced likelihood of immune escape. The robustness of the model's predictive capability was corroborated using the GEO dataset, Nomogram and an independent immunotherapy cohort. Furthermore, the model risk value was found to be significantly associated with the prognosis of LUAD patients, genomic heterogeneity, immune cell infiltration, immune regulation and immunotherapy outcomes. Additionally, we characterized the significance of the model's feature factors using single-cell clustering and pseudo-temporal analysis, revealing that the model's feature genes are predominantly located in tumor-infiltrating T cells, particularly in the exhausted and effector subtypes. TNFRSF11A emerged as a key gene in the model, promoting LUAD cell proliferation, migration, and apoptosis, and involvement in LUAD M6A methylation and PD-L1-mediated immune escape. TNFRSF11A was mainly expressed in T cell clusters and represented a potential immune system regulatory factor associated with T cell exhaustion, fostering malignant progression in LUAD cells. Our study offers new mechanistic insights and therapeutic targets for the biological behaviors and immune suppression in LUAD.
2024-09-30 | GSE270711 | GEO
Project description:Lung squamous cell carcinoma (LSCC) is the most common subtype of non-small cell lung cancer. Immunotherapy has become an effective treatment in recent years, while patients showed different responses to the current treatment. It is vital to identify the potential immunogenomic signatures to predict patient' prognosis. The expression profiles of LSCC patients with the clinical information were downloaded from TCGA database. Differentially expressed immune-related genes (IRGs) were extracted using edgeR algorithm, and functional enrichment analysis showed that these IRGs were primarily enriched in inflammatory- and immune-related processes. "Cytokine-cytokine receptor interaction" and "PI3K-AKT signaling pathway" were the most enriched KEGG pathways. 27 differentially expressed IRGs were significantly correlated with the overall survival (OS) of patients using univariate Cox regression analysis. A prognostic risk signature that comprises seven IRGs (GCCR, FGF8, CLEC4M, PTH, SLC10A2, NPPC, and FGF4) was developed with effective predictive performance by multivariable Cox stepwise regression analysis. Most importantly, the signature could be an independent prognostic predictor after adjusting for clinicopathological parameters, and also validated in two independent LSCC cohorts (GSE4573 and GSE17710). Potential molecular mechanisms and tumor immune landscape of these IRGs were investigated through computational biology. Analysis of tumor infiltrating lymphocytes and immune checkpoint molecules revealed distinct immune landscape in high- and low-risk group. The study was the first time to construct IRG-based immune signature in the recognition of disease progression and prognosis of LSCC patients.
| S-EPMC7485220 | biostudies-literature
Project description:Vulvar squamous cell carcinoma (SCC) consists of two different etiologic categories: human papilloma virus (HPV)-associated (HPV (+)) and HPV-non-associated (HPV (-)). There have been no genome-wide studies on the genetic alterations of vulvar SCCs or on the differences between HPV (+) and HPV (-) vulvar SCCs. In this study, we performed whole-exome sequencing and copy number profiling of 6 HPV (+) and 9 HPV (-) vulvar SCCs and found known mutations (TP53, CDKN2A and HRAS) and copy number alterations (CNAs) (7p and 8q gains and 2q loss) in HPV (-) SCCs. In HPV (+), we found novel mutations in PIK3CA, BRCA2 and FBXW7 that had not been reported in vulvar SCCs. HPV (-) SCCs exhibited more mutational loads (numbers of nonsilent mutations and driver mutations) than HPV (+) SCCs, but the CNA loads and mutation signatures between HPV (+) and HPV (-) SCCs did not differ. Of note, 40% and 40% of the 15 vulvar SCCs harbored PIK3CA and FAT1 alterations, respectively. In addition, we found that the SCCs harbored kataegis (a localized hypermutation) in 2 HPV (+) SCCs and copy-neutral losses of heterozygosity in 4 (one HPV (+) and 3 HPV (-)) SCCs. Our data indicate that HPV (+) and HPV (-) vulvar SCCs may have different mutation and CNA profiles but that there are genomic features common to SCCs. Our data provide useful information for both HPV (+) and HPV (-) vulvar SCCs and may aid in the development of clinical treatment strategies.
| S-EPMC5903820 | biostudies-other
Project description:BackgroundLung adenocarcinoma (LUAD) is an aggressive cancer that has an extremely poor prognosis. As well as facilitating the detachment of cancer cells from the primary tumor site, anoikis plays an important role in cancer metastasis. Few studies to date, however, have examined the role of anoikis in LUAD, in patient prognosis.MethodsA total of 316 anoikis-related genes (ANRGs) integrated from Genecards and Harmonizome portals. LUAD transcriptome data were retrieved from the Genotype-Tissue Expression Project (GEO) and The Cancer Genome Atlas (TCGA). Anoikis-related prognostic genes (ANRGs) were primarily screened by univariate Cox regression. All ANRGs were included in the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model to construct the powerful prognostic signature. This signature was validated and assessed using the Kaplan-Meier method as well as univariate and multivariate Cox regression analyses. Anoikis-related regulators of risk score were identified using a XG-boost machine learning model. The expression of ITGB4 protein was examined in a ZhengZhou University (ZZU) tissue cohort by immunohistochemistry, and the potential mechanisms of action of ITGB4 in LUAD were explored by GO, KEGG, and ingenuity pathway analyses and by GSEA.ResultsA risk score signature was constructed based on eight ANRGs, with high risk scores found to closely correlate with unfavorable clinical features. ITGB4 expression may be associated with 5-year over survival, with immunohistochemistry showed that the expression of ITGB4 was higher in LUAD than in nontumor tissues. Enrichment analysis suggested that ITGB4 may promote LUAD development by targeting E2F, MYC, and oxidative phosphorylation signaling pathways.ConclusionOur anoikis-related signature from RNA-seq data may be a novel prognostic biomarker in patients with LUAD. It may help physicians develop personalized LUAD treatments in clinical practice. Moreover, ITGB4 may affect the development of LUAD through the oxidative phosphorylation pathway.
| S-EPMC10199682 | biostudies-literature