The dynamic dysregulated network identifies stage-specific markers during lung adenocarcinoma malignant progression and metastasis

Wang, Li; Liu, Wangyang; Liu, Kailai; Wang, Lixia; Yin, Xiangzhe; Bo, Lin; Xu, Haotian; Lin, Shan; Feng, Ke; Zhou, Xinyu; Lin, Lin; Fei, Meiting; Zhang, Caiyu; Ning, Shangwei; Zhao, Hongying

doi:10.1016/j.omtn.2022.11.019

Cited by 4 publications

(2 citation statements)

References 66 publications

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“…HLA-DRB5 and CD244 play pivotal roles in controlling antigen processing and presentation, as well as T-cell activation. It has been observed that a downregulation in the expression of HLA-DRB5 correlates with a poor prognosis in LUAD ( Sun et al, 2021 ; Wu et al, 2021 ; Wang et al, 2022 ; Xu et al, 2022 ). Additionally, in NSCLC patients, CD244 has been identified as a potential negative prognostic biomarker ( Vaes et al, 2021 ).…”

Section: Resultsmentioning

confidence: 99%

Identifying potential therapeutic targets in lung adenocarcinoma: a multi-omics approach integrating bulk and single-cell RNA sequencing with Mendelian randomization

Chen,

Li,

Chang

et al. 2024

Front. Pharmacol.

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Our research aimed to identify new therapeutic targets for Lung adenocarcinoma (LUAD), a major subtype of non-small cell lung cancer known for its low 5-year survival rate of 22%. By employing a comprehensive methodological approach, we analyzed bulk RNA sequencing data from 513 LUAD and 59 non-tumorous tissues, identifying 2,688 differentially expressed genes. Using Mendelian randomization (MR), we identified 74 genes with strong evidence for a causal effect on risk of LUAD. Survival analysis on these genes revealed significant differences in survival rates for 13 of them. Our pathway enrichment analysis highlighted their roles in immune response and cell communication, deepening our understanding. We also utilized single-cell RNA sequencing (scRNA-seq) to uncover cell type-specific gene expression patterns within LUAD, emphasizing the tumor microenvironment’s heterogeneity. Pseudotime analysis further assisted in assessing the heterogeneity of tumor cell populations. Additionally, protein-protein interaction (PPI) network analysis was conducted to evaluate the potential druggability of these identified genes. The culmination of our efforts led to the identification of five genes (tier 1) with the most compelling evidence, including SECISBP2L, PRCD, SMAD9, C2orf91, and HSD17B13, and eight genes (tier 2) with convincing evidence for their potential as therapeutic targets.

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Section: Resultsmentioning

confidence: 99%

Identifying potential therapeutic targets in lung adenocarcinoma: a multi-omics approach integrating bulk and single-cell RNA sequencing with Mendelian randomization

Chen,

Li,

Chang

et al. 2024

Front. Pharmacol.

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show abstract

“…Transcriptome analysis revealed that NF-κB signaling is the downstream effector pathway of DUT, and overexpressing DUT in liver progenitor organoids conferred drug resistance to TKI Sorafenib [ 24 ]. LYPLA1 was found to be associated with poor prognosis in lung adenocarcinoma [ 25 ], while POLR2K was identified as one of the top 10 cancer immunotherapy proteins related to breast cancer by machine-learning predictions [ 26 ]. SMPD4 was also found to be a lipid metabolism-related gene associated with hepatocellular carcinoma prognosis [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Identifying prognostic markers in spatially heterogeneous breast cancer microenvironment

Liu,

Wang,

et al. 2023

J Transl Med

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To gain deeper insights into the microenvironment of breast cancer, we utilized GeoMx Digital Spatial Profiling (DSP) technology to analyze transcripts from 107 regions of interest in 65 untreated breast cancer tissue samples. Our study revealed spatial heterogeneity in the expression of marker genes in tumor cell enriched, immune cell enriched, and normal epithelial areas. We evaluated a total of 55 prognostic markers in tumor cell enriched regions and 15 in immune cell enriched regions, identifying that tumor cell enriched regions had higher levels of follicular helper T cells, resting dendritic cells, and plasma cells than immune cell enriched regions, while the levels of resting CD4 memory in T cells and regulatory (Treg) T cells were lower. Additionally, we analyzed the heterogeneity of HLA gene families, immunological checkpoints, and metabolic genes in these areas. Through univariate Cox analysis, we identified 5 prognosis-related metabolic genes. Furthermore, we conducted immunostaining experiments, including EMILIN2, SURF4, and LYPLA1, to verify our findings. Our investigation into the spatial heterogeneity of the breast cancer tumor environment has led to the discovery of specific diagnostic and prognostic markers in breast cancer.

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Disfunction of communication among immune cells in minimal-deviation adenocarcinoma of the cervix as an immunotherapeutic opportunity

Zhang,

Liu,

Zhai

et al. 2023

International Immunopharmacology

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The dynamic dysregulated network identifies stage-specific markers during lung adenocarcinoma malignant progression and metastasis

Cited by 4 publications

References 66 publications

Identifying potential therapeutic targets in lung adenocarcinoma: a multi-omics approach integrating bulk and single-cell RNA sequencing with Mendelian randomization

Identifying potential therapeutic targets in lung adenocarcinoma: a multi-omics approach integrating bulk and single-cell RNA sequencing with Mendelian randomization

Identifying prognostic markers in spatially heterogeneous breast cancer microenvironment

Disfunction of communication among immune cells in minimal-deviation adenocarcinoma of the cervix as an immunotherapeutic opportunity

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