Identification of prognostic candidate signatures by systematically revealing transcriptome characteristics in lung adenocarcinoma with differing tumor microenvironment immune phenotypes

Chen, Qiang; Ma, Jiakang; Wang, Xiaoyi; Zhu, Xiaoyan

doi:10.18632/aging.204112

Cited by 4 publications

(3 citation statements)

References 60 publications

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“…Subsequently, we conducted batch differential analysis, which led to the identification of FGR , PSMD14 , and ZBTB16 as differentially expressed genes exhibiting prognostic significance. Several studies have been observed that these genes are involved in the oncogenesis of LUAD ( 58 - 61 ). In addition, our analysis revealed a marked downregulation in the expression of FGR and ZBTB16 , whereas the expression of PSMD14 was significantly upregulated in LUAD.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis and single-cell RNA sequencing: elucidating the ubiquitination pathways and key enzymes in lung adenocarcinoma

Lu¹,

Xu²,

Wang³

et al. 2023

J Thorac Dis

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Background Lung adenocarcinoma (LUAD) is a prevalent subtype of lung cancer associated with high mortality rates. We aimed to utilize single-cell multiomics analysis to identify the key molecules involved in ubiquitination modification, which plays a role in LUAD development and progression. Methods We use a systematic approach to analyze LUAD-related single-cell and bulk transcriptome datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Single-cell RNA sequencing (scRNA-seq) data were normalized, clustered, and annotated with the Seurat package in R. InferCNV was used to distinguish malignant from epithelial cells, and AUCell evaluated the area under the curve (AUC) score of ubiquitination-related enzymes. Survival and differential analyses identified significant molecular markers associated with ubiquitination. PSMD14 expression was confirmed using reverse-transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot assays, and its knockdown cell lines were assessed for effects on cellular processes and tumor formation in mice. PSMD14 ’s interacting proteins were predicted, and its impact on AGR2 protein half-life and ubiquitination was evaluated. Rescue experiments involving PSMD14 overexpression and AGR2 silencing assessed their impact on malignant behaviors. Results By means of single-cell sequencing analysis, we probed the ubiquitination modification landscape in the LUAD microenvironment. Malignant cells had elevated scores for enzymes and ubiquitin-binding domains compared to normal epithelial cells, with 53 ubiquitination-related molecules showing prognostic disparities. FGR , PSMD14 , and ZBTB16 were identified as genes with prognostic significance, with PSMD14 showing higher expression in epithelial and malignant cells. Two missense mutation sites were identified in PSMD14 , which had a high copy number amplification ratio and positive correlation with messenger RNA (mRNA) expression. PSMD14 expression and tumor stage were found to be independent prognostic factors, and interfering with PSMD14 expression reduced the malignant behavior of LUAD cells. PSMD14 was found to bind to AGR2 protein and reduce its ubiquitination, leading to increased AGR2 stability. Knockdown of AGR2 inhibited the enhancement of cell viability, invasion, and migration resulting from PSMD14 overexpression. Conclusions This study examined ubiquitination modifications in LUAD using sequencing data, identifying PSMD14 ’s critical role in malignancy re...

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Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis and single-cell RNA sequencing: elucidating the ubiquitination pathways and key enzymes in lung adenocarcinoma

Lu¹,

Xu²,

Wang³

et al. 2023

J Thorac Dis

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“…Furthermore, the risk score based on the six-gene signature was significantly correlated with immunological status of LUAD patients. It is well known that tumor immune microenvironment (TIME) plays important roles in cancer biology, and patients with differing TIME present differing immunotherapeutic responses and clinical outcomes [ 86 – 88 ]. Tumor immunophenotype has been gradually recognized as an independent prognostic factor to estimate the prognosis [ 89 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is well known that tumor immune microenvironment (TIME) plays important roles in cancer biology, and patients with differing TIME present differing immunotherapeutic responses and clinical outcomes [86][87][88].…”

Section: Discussionmentioning

confidence: 99%

A robust six-gene prognostic signature based on two prognostic subtypes constructed by chromatin regulators is correlated with immunological features and therapeutic response in lung adenocarcinoma

Chen,

Zhao,

2023

Aging

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Accumulating evidence has demonstrated that chromatin regulators (CRs) regulate immune cell infiltration and are correlated with prognoses of patients in some cancers. However, the immunological and prognostic roles of CRs in lung adenocarcinoma (LUAD) are still unclear. Here, we systematically revealed the correlations of CRs with immunological features and the survival in LUAD patients based on a cohort of gene expression datasets from the public TCGA and GEO databases and real RNA-seq data by an integrative analysis using a comprehensive bioinformatics method. Totals of 160 differentially expressed CRs (DECRs) were identified between LUAD and normal lung tissues, and two molecular prognostic subtypes (MPSs) were constructed and evaluated based on 27 prognostic DECRs using five independent datasets ( p =0.016, <0.0001, =0.008, =0.00038 and =0.00055, respectively). Six differentially expressed genes (DEGs) ( CENPK , ANGPTL4 , CCL20 , CPS1 , GJB3 , TPSB2 ) between two MPSs had the most important prognostic feature and a six-gene prognostic model was established. LUAD patients in the low-risk subgroup showed a higher overall survival (OS) rate than those in the high-risk subgroup in nine independent datasets ( p <0.0001, =0.021, =0.016, =0.0099, <0.0001, =0.0045, <0.0001, =0.0038 and =0.00013, respectively). Six-gene prognostic signature had the highest concordance index of 0.673 compared with 19 reported prognostic signatures. The risk score was significantly correlated with immunological features and activities of oncogenic signaling pathways. LUAD patients in the low-risk subgroup benefited more from immunotherapy and were less sensitive to conventional chemotherapy agents. This study provides novel insights into the prognostic and immunological roles of CRs in LUAD.

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Integrating bulk-RNA sequencing and single-cell sequencing analyses to characterize adenosine-enriched tumor microenvironment landscape and develop an adenosine-related prognostic signature predicting immunotherapy in lung adenocarcinoma

Han,

Wu,

Liu

et al. 2024

Funct Integr Genomics

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Identification of prognostic candidate signatures by systematically revealing transcriptome characteristics in lung adenocarcinoma with differing tumor microenvironment immune phenotypes

Cited by 4 publications

References 60 publications

Bioinformatics analysis and single-cell RNA sequencing: elucidating the ubiquitination pathways and key enzymes in lung adenocarcinoma

Bioinformatics analysis and single-cell RNA sequencing: elucidating the ubiquitination pathways and key enzymes in lung adenocarcinoma

A robust six-gene prognostic signature based on two prognostic subtypes constructed by chromatin regulators is correlated with immunological features and therapeutic response in lung adenocarcinoma

Integrating bulk-RNA sequencing and single-cell sequencing analyses to characterize adenosine-enriched tumor microenvironment landscape and develop an adenosine-related prognostic signature predicting immunotherapy in lung adenocarcinoma

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