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Prognostic significance of ABCB1 in stage I lung adenocarcinoma.

ABSTRACT: Cancer stem cell (CSC) properties have been recently proposed to explain tumor carcinogenesis and multidrug resistance in several human cancers, including non-small cell lung cancer (NSCLC). The present study examined the protein expression of three CSC-associated markers, namely ATP binding cassette subfamily B member 1 (ABCB1), aldehyde dehydrogenase 1 family member A1 (ALDH1A1) and cluster of differentiation (CD) 44, by immunohistochemistry in 194 NSCLC patients who underwent complete resection of NSCLC tumors. The association between the expression of these proteins and patient prognosis was evaluated to clarify the prognostic significance of CSC-associated markers in NSCLC patients. Positive staining for ABCB1 demonstrated a trend toward worse survival compared with negative staining in stage I-III NSCLC. Negative staining for ALDH1 or CD44 exhibited a trend toward worse survival compared with positive staining in stage I-III NSCLC. It was observed that patients with stage I lung adenocarcinoma (ADC) showing positivity for ABCB1 expression had significantly poorer survival than those with negative ABCB1 staining (P=0.03). Furthermore, stage I ADC patients with wild-type epidermal growth factor receptor (EGFR) who exhibited positive staining for ABCB1 had significantly shorter disease-free survival (DFS) compared with patients with negative staining for ABCB1 (P<0.01). Analyses by univariate and multivariate Cox proportional hazards models revealed that ABCB1-positive staining was significantly associated with DFS and was an independent prognostic factor (hazard ratio, 3.49; P<0.05) in these patients. These results suggest that ABCB1 protein expression is useful for predicting prognosis and selecting patients for post-operative therapy in stage I lung ADC patients, particularly those harboring wild-type EGFR.

SUBMITTER: Zou F

PROVIDER: S-EPMC5494850 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Project description:BackgroundRecent studies have demonstrated that upregulation of heat shock transcription factor 2 binding protein (HSF2BP) may promote genomic instability, thereby leading to the development of tumors and also providing a potential target for biological antitumor therapy. However, the role of HSF2BP has so far remained unclear in lung adenocarcinoma (LUAD).MethodsTo explore the function of HSF2BP in LUAD, we collected transcriptome data for 551 lung samples from The Cancer Genome Atlas (TCGA) database and methylation data for 461 lung samples from the University of California Santa Cruz (UCSC) genome database, in addition to corresponding clinical information. We used bioinformatic approaches to systematically explore the role of HSF2BP in LUAD, including Gene Set Enrichment Analysis (GSEA), coexpression analysis, the Tumor IMmune Estimation Resource (TIMER) tool, Connectivity Map (CMap) analysis, and a meta-analysis involving three Gene Expression Omnibus (GEO) datasets and one TCGA dataset.ResultsOur results found that upregulation of HSF2BP in LUAD was an independent risk factor for the prognosis and diagnosis of LUAD. GSEA analysis showed HSF2BP expression was associated with vital signaling pathways, including the cell cycle, P53 signaling pathway, and homologous recombination. Coexpression analysis revealed 10 HSF2BP-associated genes, including oncogenes and tumor suppressor genes. Additionally, we found that HSF2BP expression was negatively correlated with B-cell infiltration and had a potential interaction with CD80 in LUAD, which may play an important role in tumor immune escape. Finally, we identified four small-molecule drugs which show promise for LUAD treatment.ConclusionsThe present study found that elevated HSF2BP posed a threat to prognosis in LUAD patients. HSF2BP might have been involved in tumorigenesis by influencing genomic stability and contributing to tumor immune evasion in the tumor immune microenvironment of LUAD. These findings suggest that HSF2BP may provide a vulnerable target for improving and enhancing treatment of LUAD.

Project description:BackgroundNumerous studies have revealed that the abnormal expression of pyroptosis-related genes is closely related to the prognosis of lung adenocarcinoma (LUAD); however, a comprehensive analysis has yet to be conducted. This study aimed to reveal the influence of pyroptosis-related genes on the prognosis of LUAD and establish a prognostic model based on those genes, in order to evaluate the prognosis of LUAD.MethodsThe data of tumor and normal samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differential analysis was used to identify pyroptosis-related genes (obtained from the GeneCards database) that were differentially expressed (DE) in TCGA database. Univariate and stepwise multivariate Cox proportional hazards regression analyses were used to screen feature genes related to LUAD overall survival (OS) and construct gene signature. Gene set enrichment analysis (GSEA) was then performed to reveal potential functions related to gene signature. Finally, the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was used to reveal distinctions in each cell-subtype groups in the immune landscape of LUAD.ResultsOverall, 26 DE genes (DEGs) associated with pyroptosis were obtained. Among them, 4 (MKI67, BTK, MST1, and TUBB6) were selected as prognostic genes and a 4-gene signature with a good prognostic performance in the TCGA and GEO was constructed. The gene signature was shown to be an independent prognostic factor of LUAD in subsequent analysis. Functional enrichment indicated that the 4-gene signature may participate in the tumorigenesis and development of LUAD through various pathways related to tumor progression to play a prognostic role in LUAD. Additionally, the results of the immune landscape indicated that the 4-gene signature may affect the prognosis of LUAD via cooperating with changes in the immune microenvironment.ConclusionsThe key biomarkers and pathways identified in this study would deepen the comprehension of the molecular mechanism of pyroptosis in LUAD. More importantly, the 4-gene signature may serve as a novel potential prognostic model for LUAD.

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Prognostic significance of ABCB1 in stage I lung adenocarcinoma.

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