Identification of an inflammatory response signature associated with prognostic stratification and drug sensitivity in lung adenocarcinoma

Song, Congkuan; Lu, Zilong; Lai, Kai; Li, Donghang; Hao, Bo; Xu, Chenzhen; Pan, Shize; Li, Ning; Geng, Qing

doi:10.1038/s41598-022-14323-6

Cited by 4 publications

(4 citation statements)

References 56 publications

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“…No significant difference was observed in PTPRE expression in different sexes of patients, but expression displayed a weak correlation with patient age [13]. In lung adenocarcinoma, PTPRE was suggested as one of the genes potentially helpful to categorize different prognostic and therapeutic subgroups [29]. Overexpression of PTPRE was likewise reported for all stages of renal cell carcinoma [14].…”

Section: Discussionmentioning

confidence: 99%

Role of Protein Tyrosine Phosphatase Receptor Type E (PTPRE) in Chemoresistant Retinoblastoma

Mohren,

Doege,

Miroschnikov

et al. 2024

IJMS

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Protein tyrosine phosphatase receptor type E (PTPRE) is a member of the “classical” protein tyrosine phosphatase subfamily and regulates a variety of cellular processes in a tissue-specific manner by antagonizing the function of protein tyrosine kinases. PTPRE plays a tumorigenic role in different human cancer cells, but its role in retinoblastoma (RB), the most common malignant eye cancer in children, remains to be elucidated. Etoposide-resistant RB cell lines and RB patients display significant higher PTPRE expression levels compared to chemosensitive counterparts and the healthy human retina, respectively. PTPRE promotor methylation analyses revealed that PTPRE expression in RB is not regulated via this mechanism. Lentiviral PTPRE knockdown (KD) induced a significant decrease in growth kinetics, cell viability, and anchorage-independent growth of etoposide-resistant Y79 and WERI RB cells. Caspase-dependent apoptosis rates were significantly increased and a re-sensitization for etoposide could be observed after PTPRE depletion. In vivo chicken chorioallantoic membrane (CAM) assays revealed decreased tumor formation capacity as well as reduced tumor size and weight following PTPRE KD. Expression levels of miR631 were significantly downregulated in etoposide-resistant RB cells and patients. Transient miR631 overexpression resulted in significantly decreased PTPRE levels and concomitantly decreased proliferation and increased apoptosis levels in etoposide-resistant RB cells. These impacts mirror PTPRE KD effects, indicating a regulation of PTPRE via this miR. Additionally, PTPRE KD led to altered phosphorylation of protein kinase SGK3 and—dependent on the cell line—AKT and ERK1/2, suggesting potential PTPRE downstream signaling pathways. In summary, these results indicate an oncogenic role of PTPRE in chemoresistant retinoblastoma.

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Section: Discussionmentioning

confidence: 99%

Role of Protein Tyrosine Phosphatase Receptor Type E (PTPRE) in Chemoresistant Retinoblastoma

Mohren,

Doege,

Miroschnikov

et al. 2024

IJMS

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“…Three independent LUAD cohorts were collected from the GEO database ( https://www.ncbi.nlm.nih.gov/geo/ ) asexternal validations, respectively, GSE68465 ( n = 443) ( Shedden et al, 2008 ), GSE72094 (n = 442) ( Schabath et al, 2016 ), and GSE31210 ( n = 226) ( Okayama et al, 2012 ; Yamauchi et al, 2012 ). For processing the GEO data, we refer to the method of ( Song et al 2022 ). The LUAD GEO dataset included in this study was mainly considered based on the sample size.…”

Section: Methodsmentioning

confidence: 99%

“…Lung cancer is the most common malignant tumor of the respiratory system, and the basic and clinical research on lung cancer is increasingly attracting attention ( Mok et al, 2019 ; Song et al, 2020 ; Song et al, 2022 ). Although the current research on the pathogenesis of lung cancer has made great progress, but the clinical treatment effect of lung cancer is still not satisfactory, and the long-term survival rate of lung cancer still has great room for improvement.…”

Section: Introductionmentioning

confidence: 99%

Integrated analysis of bulk and single-cell RNA-seq reveals the role of MYC signaling in lung adenocarcinoma

Lü¹,

Chen²,

Chen

et al. 2022

Front. Genet.

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MYC is one of the well-known oncogenes, and its important role in cancer still remains largely unknown. We obtained lung adenocarcinoma (LUAD) multi-omics data including genome, transcriptome, and single-cell sequencing data from multiple cohorts. We calculated the GSVA score of the MYC target v1 using the ssGSEA method, and obtained the genes highly correlated with this score by Spearman correlation analysis. Subsequent hierarchical clustering divided these genes into two gene sets highly associated with MYC signaling (S1 and S2). Unsupervised clustering based on these genes divided the LUAD samples into two distinct subgroups, namely, the MYC signaling inhibition group (C1) and activation group (C2). The MCP counter package in R was used to assess tumor immune cell infiltration abundance and ssGSEA was used to calculate gene set scores. The scRNA-seq was used to verify the association of MYC signaling to cell differentiation. We observed significant differences in prognosis, clinical characteristics, immune microenvironment, and genomic alterations between MYC signaling inhibition and MYC signaling activation groups. MYC-signaling is associated with genomic instability and can mediate the immunosuppressive microenvironment and promote cell proliferation, tumor stemness. Moreover, MYC-signaling activation is also subject to complex post-transcriptional regulation and is highly associated with cell differentiation. In conclusion, MYC signaling is closely related to the genomic instability, genetic alteration and regulation, the immune microenvironment landscape, cell differentiation, and disease survival in LUAD. The findings of this study provide a valuable reference to revealing the mechanism of cancer-promoting action of MYC in LUAD.

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“…Despite appropriate surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, the 5-year survival of lung cancer patients is still only 16.8%, the prognosis of most LUAD patients remains suboptimal [ 3 ]. In addition, the complex pathogenesis of LUAD leads to inaccurate prediction of patient prognosis according to the current TNM staging system [ 4 ]. Therefore, it is urgent to decipher the tumorigenesis of LUAD and discover effective biomarkers and potential therapeutic targets to predict the prognosis of LUAD patients.…”

Section: Introductionmentioning

confidence: 99%

Identification of four metabolic subtypes and key prognostic markers in lung adenocarcinoma based on glycolytic and glutaminolytic pathways

Zhang

Wang²,

Song³

et al. 2023

BMC Cancer

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Background Glucose and glutamine are the main energy sources for tumor cells. Whether glycolysis and glutaminolysis play a critical role in driving the molecular subtypes of lung adenocarcinoma (LUAD) is unknown. This study attempts to identify LUAD metabolic subtypes with different characteristics and key genes based on gene transcription profiling data related to glycolysis and glutaminolysis, and to construct prognostic models to facilitate patient outcome prediction. Methods LUAD related data were obtained from the Cancer Genome Atlas and Gene Expression Omnibus, including TCGA-LUAD, GSE42127, GSE68465, GSE72094, GSE29013, GSE31210, GSE30219, GSE37745, GSE50081. Unsupervised consensus clustering was used for the identification of LUAD subtypes. Differential expression analysis, weighted gene co-expression network analysis (WGCNA) and CytoNCA App in Cytoscape 3.9.0 were used for the screening of key genes. The Cox proportional hazards model was used for the construction of the prognostic risk model. Finally, qPCR analysis, immunohistochemistry and immunofluorescence colocalization were used to validate the core genes of the model. Result This study identified four distinct characterized LUAD metabolic subtypes, glycolytic, glutaminolytic, mixed and quiescent types. The glycolytic type had a worse prognosis than the glutaminolytic type. Nine genes (CXCL8, CNR1, AGER, ALB, S100A7, SLC2A1, TH, SPP1, LEP) were identified as hub genes driving the glycolytic/glutaminolytic LUAD. In addition, the risk assessment model constructed based on three genes (SPP1, SLC2A1 and AGER) had good predictive performance and could be validated in multiple independent external LUAD cohorts. These three genes were differentially expressed in LUAD and lung normal tissues, and might be potential prognostic markers for LUAD. Conclusion LUAD can be classified into four different characteristic metabolic subtypes based on the glycolysis- and glutaminolysis-related genes. Nine genes (CXCL8, CNR1, AGER, ALB, S100A7, SLC2A1, TH, SPP1, LEP) may play an important role in the subtype-intrinsic drive. This metabolic subtype classification, provides new biological insights into the previously established LUAD subtypes.

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Identification of an inflammatory response signature associated with prognostic stratification and drug sensitivity in lung adenocarcinoma

Cited by 4 publications

References 56 publications

Role of Protein Tyrosine Phosphatase Receptor Type E (PTPRE) in Chemoresistant Retinoblastoma

Role of Protein Tyrosine Phosphatase Receptor Type E (PTPRE) in Chemoresistant Retinoblastoma

Integrated analysis of bulk and single-cell RNA-seq reveals the role of MYC signaling in lung adenocarcinoma

Identification of four metabolic subtypes and key prognostic markers in lung adenocarcinoma based on glycolytic and glutaminolytic pathways

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