Gene expression profile of EGFRwt/KRASwt/ALKwt lung adenocarcinoma (“pan-driver-gene-negative” LUAD) and developing a prognostic signature for “pan-driver-gene-negative” LUAD
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PROVIDER: PRJNA473511 | ENA |
REPOSITORIES: ENA
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Project description:For developing a accurate prognostic signature for “pan-driver-gene-negative” LUAD, we employed whole genome microarray expression profiling as a discovery platform to identify candidate genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis based on whole-genome microarrays indicated that the Wnt/β-catenin pathway was activated in “pan-driver-gene-negative” LUAD. Furthermore, the Wnt/β-catenin-pathway-based gene expression profiles revealed 39 transcripts differentially expressed by diagnostic status, with 30 genes being upregulated and 9 downregulated. Finally, a Wnt/β-catenin-pathway-based signature (CSDW) comprising 4 genes (β-catenin, Wnt2b, DVL3 and SOX9) was developed to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter overall survival (hazard ratio [HR] 10·42, 6·46–16·79; p<0·001) than patients with low-risk scores. The CSDW performance was further validated in an internal cohort and two external cohorts. The protein expression levels of several hub genes, including β-catenin, SOX9, DVL3 and Wnt2b, were strongly correlated with lymphatic metastasis and distant organ metastasis. Furthermore, a nomogram comprising CSDW and other variables was generated to predict progression-free survival and overall survival in the training cohort and performed well in the three independent validation cohorts (C-index: 0·725, 0·697 and 0·693, respectively). For developing a accurate prognostic signature for “pan-driver-gene-negative” LUAD, we employed whole genome microarray expression profiling as a discovery platform to identify candidate genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis based on whole-genome microarrays indicated that the Wnt/β-catenin pathway was activated in “pan-driver-gene-negative” LUAD. Furthermore, the Wnt/β-catenin-pathway-based gene expression profiles revealed 39 transcripts differentially expressed by diagnostic status, with 30 genes being upregulated and 9 downregulated. Finally, a Wnt/β-catenin-pathway-based signature (CSDW) comprising 4 genes (β-catenin, Wnt2b, DVL3 and SOX9) was developed to classify patients into high-risk and low-risk groups in the training cohort. Patients with high-risk scores in the training cohort had shorter overall survival (hazard ratio [HR] 10·42, 6·46–16·79; p<0·001) than patients with low-risk scores. The CSDW performance was further validated in an internal cohort and two external cohorts. The protein expression levels of several hub genes, including β-catenin, SOX9, DVL3 and Wnt2b, were strongly correlated with lymphatic metastasis and distant organ metastasis. Furthermore, a nomogram comprising CSDW and other variables was generated to predict progression-free survival and overall survival in the training cohort and performed well in the three independent validation cohorts (C-index: 0·725, 0·697 and 0·693, respectively).
2021-01-08 | GSE115002 | GEO
Project description:Circulating tumor cells (CTCs) represent the molecular characteristics of tumor sites and travel in the blood for seeding distant metastases. "EpCAM+/pan-cytokeratin (CK)+/CD45-/DAPI+" has been widely accepted as a CTC definition, especially in breast cancer, prostate cancer and colorectal cancer. However, reports on CTC detection in non-small cell lung cancer are limited due to a lack of efficient CTC marker. We describe hexokinase 2 (HK2) that assays elevated glycolysis of cancer cells, called Warburg effect, as a new marker for CTC detection in lung adenocarcinoma (LUAD), especially the CK negative CTCs. Single-cell sequencing was used to confirm the malignancy of putative CTCs by detecting genome-wide copy number alternations characteristic of malignant cells. We employed this marker in a variety of liquid biopsies from LUAD patients, including peripheral blood, pleural effusion and cerebrospinal fluid.
2021-02-28 | E-MTAB-8767 | biostudies-arrayexpress
Project description:BackgroundTo study the role of computed tomography (CT)-derived radiomics features and clinical characteristics on the prognosis of "driver gene-negative" lung adenocarcinoma (LUAD) and to explore the potential molecular biological which may be helpful for patients' individual postoperative care.MethodsA total of 180 patients with stage I-III "driver gene-negative" LUAD in the First Affiliated Hospital of Sun Yat-Sen University from September 2003 to June 2015 were retrospectively collected. The Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model was used to screen radiomics features and calculated the Rad-score. The prediction performance of the nomogram model based on radiomics features and clinical characteristics was validated and then assessed with respect to calibration. Gene set enrichment analysis (GSEA) was used to explore the relevant biological pathways.ResultsThe radiomics and the clinicopathological characteristics were combined to construct a nomogram resulted in better performance for the estimation of OS (C-index: 0.815; 95% confidence interval [CI]: 0.756-0.874) than the clinicopathological nomogram (C-index: 0.765; 95% CI: 0.692-0.837). Decision curve analysis demonstrated that in terms of clinical usefulness, the radiomics nomogram outperformed the traditional staging system and the clinicopathological nomogram. The clinical prognostic risk score of each patient was calculated based on the radiomics nomogram and divided by X-tile into high-risk (> 65.28) and low-risk (≤ 65.28) groups. GSEA results showed that the low-risk score group was directly related to amino acid metabolism, and the high-risk score group was related to immune and metabolism pathways.ConclusionsThe radiomics nomogram was promising to predict the prognosis of patients with "driver gene-negative" LUAD. The metabolism and immune-related pathways may provide new treatment orientation for this genetically unique subset of patients, which may serve as a potential tool to guide individual postoperative care for those patients.
| S-EPMC10264479 | biostudies-literature
Project description:Single-cell analysis identifies PLK1 as a driver of immunosuppressive tumor microenvironment in LUAD
| PRJNA1103932 | ENA
Project description:PLK1 (Polo-like kinase 1) plays a critical role in the progression of lung adenocarcinoma (LUAD). Recent studies have unveiled that targeting PLK1 improves the efficacy of immunotherapy, highlighting its important role in the regulation of tumor immunity. Nevertheless, our understanding of the intricate interplay between PLK1 and the tumor microenvironment (TME) remains incomplete. Here, using genetically engineered mouse model and single-cell RNA-seq analysis, we report that PLK1 promotes an immunosuppressive TME in LUAD, characterized with enhanced M2 polarization of tumor associated macrophages (TAM) and dampened antigen presentation process. Mechanistically, elevated PLK1 coincides with increased secretion of CXCL2 cytokine, which promotes M2 polarization of TAM and diminishes expression of class II major histocompatibility complex (MHC-II) in professional antigen-presenting cells. Furthermore, PLK1 negatively regulates MHC-II expression in cancer cells, which has been shown to be associated with compromised tumor immunity and unfavorable patient outcomes. Taken together, our results reveal PLK1 as a novel modulator of TME in LUAD and provide possible therapeutic interventions.
2024-05-28 | GSE264739 | GEO
Project description:For in-depth characterization of neuroendocrine transformation, we analyzed clinical specimens consisting of combined lung adenocarcinoma (LUAD)/small cell lung carcinoma (SCLC) histology exhibiting clear spatial separation. Microdissection was performed for RNA sequencing.
2021-06-03 | E-MTAB-10399 | biostudies-arrayexpress
Project description:Circ101093 was knocked down in A549 LUAD cell lines, and overexpressed in H1975 LUAD cell lines. Then, downregulated proteins in A549 cell lines and upregulated proteins in H1975 cell lines were analyzed.
2022-05-20 | PXD025491 | Pride
Project description:To define the molecular underpinning of bone metastasis in pan-cancer, we performed high-throughput transcriptome sequencing (RNA-seq) using total RNA from veterbral metatases of LUAD, BRCA, PRAD, SCRA, LIHC, SKCM, THYM, etc. tissues. Afterwards, expression profile were used for further analysis.
2025-06-01 | GSE273023 | GEO
Project description:To define the molecular underpinning of bone metastasis in pan-cancer, we performed high-throughput transcriptome sequencing (RNA-seq) using total RNA from veterbral metatases of LUAD, BRCA, PRAD, SCRA, LIHC, SKCM, THYM, etc. tissues. Afterwards, expression profile were used for further analysis.
2025-06-01 | GSE274442 | GEO
Project description:IGF2BP3, an oncofetal protein and an m6A reader, is a member of the IGF2BPs family playing an important role in cell migration in early embryogenesis, oncogenesis, metabolism and metastasis. To clarify the effect of depletion of IGF2BP3 on gene expression in LUAD, we conducted IGF2BP3 knocked out experiments in the NCI-H1299 LUAD cell lines. The knockout efficiency was validated by western blot analysis, demonstrating successful silencing of IGF2BP3 at the protein levels in NCI-H1299 cells. To explore the underlying mechanisms of IGF2BP3 in LUAD development, we conducted RNA-sequencing analysis using IGF2BP3 knockout and control NCI-H1299 cells, with each group consisting of three biological replicates. The analysis revealed that IGF2BP3 knockout resulted in differential expression of 1700 genes including 621 genes upregulated and 1079 downregulated.
2025-04-09 | GSE270702 | GEO