Expression patterns and clinical significances of PBK in lung cancer: an analysis based on Oncomine database

: MicroRNAs (miRNAs) are highly conserved non-coding RNAs involved in many physiological processes such as cell proliferation, inhibition, development of apoptosis, differentiation, suppresses tumorigenicity, and regulating cell growth. The description of the alterations of miRNA expression patterns in cancers will be helpful to recognize biomarkers for early detection and possible therapeutic intervention in the treatment of cancers. Recent studies have shown that miR-451 is broadly dysregulated in lung cancer and is a crucial agent in lung tumor progression. This review summarizes recent advances of the potential role of miR-451 in lung cancer diagnosis, prognosis, and treatment and provides an insight into the potential use of miR-451 for the development of advanced therapeutic methods in lung cancer.

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Gene expression profiling of epigenetic chromatin modification enzymes and histone marks by cigarette smoke: implications for COPD and lung cancer

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00253.2016 ◽

2016 ◽

Vol 311 (6) ◽

pp. L1245-L1258 ◽

Cited By ~ 19

Author(s):

Isaac K. Sundar ◽

Irfan Rahman

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Dna Methylation ◽

Cigarette Smoke ◽

Histone Modifications ◽

Expression Patterns ◽

Chromatin Modification ◽

Gene Expression Patterns ◽

Validation Data ◽

Histone Marks

Chromatin-modifying enzymes mediate DNA methylation and histone modifications on recruitment to specific target gene loci in response to various stimuli. The key enzymes that regulate chromatin accessibility for maintenance of modifications in DNA and histones, and for modulation of gene expression patterns in response to cigarette smoke (CS), are not known. We hypothesize that CS exposure alters the gene expression patterns of chromatin-modifying enzymes, which then affects multiple downstream pathways involved in the response to CS. We have, therefore, analyzed chromatin-modifying enzyme profiles and validated by quantitative real-time PCR (qPCR). We also performed immunoblot analysis of targeted histone marks in C57BL/6J mice exposed to acute and subchronic CS, and of lungs from nonsmokers, smokers, and patients with chronic obstructive pulmonary disease (COPD). We found a significant increase in expression of several chromatin modification enzymes, including DNA methyltransferases, histone acetyltransferases, histone methyltransferases, and SET domain proteins, histone kinases, and ubiquitinases. Our qPCR validation data revealed a significant downregulation of Dnmt1, Dnmt3a, Dnmt3b, Hdac2, Hdac4, Hat1, Prmt1, and Aurkb. We identified targeted chromatin histone marks (H3K56ac and H4K12ac), which are induced by CS. Thus CS-induced genotoxic stress differentially affects the expression of epigenetic modulators that regulate transcription of target genes via DNA methylation and site-specific histone modifications. This may have implications in devising epigenetic-based therapies for COPD and lung cancer.

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O-256 Prognostic significance Brm expression patterns in non-small cell lung cancer (NSCLC)

Lung Cancer ◽

10.1016/s0169-5002(03)91914-3 ◽

2003 ◽

Vol 41 ◽

pp. S75

Author(s):

Junya Fukuoka ◽

Joanna Shih ◽

Stephane Hewitt ◽

William D. Travis ◽

Jin Jen

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Expression Patterns ◽

Prognostic Significance ◽

Small Cell ◽

Small Cell Lung

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A lepidic gene signature predicts patient prognosis and sensitivity to immunotherapy in lung adenocarcinoma

Genome Medicine ◽

10.1186/s13073-021-01010-w ◽

2022 ◽

Vol 14 (1) ◽

Author(s):

Thinh T. Nguyen ◽

Hyun-Sung Lee ◽

Bryan M. Burt ◽

Jia Wu ◽

Jianjun Zhang ◽

...

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Lung Adenocarcinoma ◽

Gene Expression Analysis ◽

Immune Cell ◽

Expression Patterns ◽

Immune Cell Infiltration ◽

Histological Subtypes ◽

Genomic Features ◽

Differential Gene

Abstract Background Lung adenocarcinoma, the most common type of lung cancer, has a high level of morphologic heterogeneity and is composed of tumor cells of multiple histological subtypes. It has been reported that immune cell infiltration significantly impacts clinical outcomes of patients with lung adenocarcinoma. However, it is unclear whether histologic subtyping can reflect the tumor immune microenvironment, and whether histologic subtyping can be applied for therapeutic stratification of the current standard of care. Methods We inferred immune cell infiltration levels using a histological subtype-specific gene expression dataset. From differential gene expression analysis between different histological subtypes, we developed two gene signatures to computationally determine the relative abundance of lepidic and solid components (denoted as the L-score and S-score, respectively) in lung adenocarcinoma samples. These signatures enabled us to investigate the relationship between histological composition and clinical outcomes in lung adenocarcinoma using previously published datasets. Results We found dramatic immunological differences among histological subtypes. Differential gene expression analysis showed that the lepidic and solid subtypes could be differentiated based on their gene expression patterns while the other subtypes shared similar gene expression patterns. Our results indicated that higher L-scores were associated with prolonged survival, and higher S-scores were associated with shortened survival. L-scores and S-scores were also correlated with global genomic features such as tumor mutation burdens and driver genomic events. Interestingly, we observed significantly decreased L-scores and increased S-scores in lung adenocarcinoma samples with EGFR gene amplification but not in samples with EGFR gene mutations. In lung cancer cell lines, we observed significant correlations between L-scores and cell sensitivity to a number of targeted drugs including EGFR inhibitors. Moreover, lung cancer patients with higher L-scores were more likely to benefit from immune checkpoint blockade therapy. Conclusions Our findings provided further insights into evaluating histology composition in lung adenocarcinoma. The established signatures reflected that lepidic and solid subtypes in lung adenocarcinoma would be associated with prognosis, genomic features, and responses to targeted therapy and immunotherapy. The signatures therefore suggested potential clinical translation in predicting patient survival and treatment responses. In addition, our framework can be applied to other types of cancer with heterogeneous histological subtypes.

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Comprehensive Analysis of the Expression and Prognosis for IRXs in Non-small Cell Lung Cancer

10.21203/rs.3.rs-78198/v1 ◽

2020 ◽

Author(s):

Qiongzi Wang ◽

Xueshan Qiu

Keyword(s):

Lung Cancer ◽

Human Lung ◽

Expression Patterns ◽

Human Lung Cancer ◽

Prognostic Indicators ◽

Normal Lung ◽

Kaplan Meier ◽

Go Enrichment ◽

Cancer Tissues ◽

Kaplan Meier Plotter

Abstract Iroquoishomeobox transcription factor family （IRXs）have been increasingly reported to play roles in suppressing or promoting a variety of cancers, however, little is known about their expression and prognostic value in terms of human lung cancer. In this study, Oncomine, GEPIA, Kaplan-Meier plotter, and cBioPortal databases were used to analyze the different expression patterns and prognostic values of six IRXs in NSCLC and examine their related functions and pathways using GO enrichment. Compared with normal lung cancer tissues, the expression of IRX1 and IRX2 in NSCLC tissues was significantly lower and was positively correlated with the 10-year survival rate of patients. Higher expression of IRX4 was related to terminal tumors, and suggested a poor prognosis. It was also found that IRXs may play a tumor-suppressive role in the localization of cytoplasm in NSCLC, while localization in the nucleus suggests a more malignant behavior. Together these results suggest that IRX1 and IRX2 may be prognostic indicators of LUAD, and that IRX4 could be a potential target for LUAD treatment.

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Gene Expression Patterns, Prognostic and Diagnostic Markers, and Lung Cancer Biology

CHEST Journal ◽

10.1378/chest.125.5_suppl.111s-a ◽

2004 ◽

Vol 125 (5) ◽

pp. 111S-115S ◽

Cited By ~ 11

Author(s):

Naftali Kaminski ◽

Meir Krupsky

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Cancer Biology ◽

Expression Patterns ◽

Diagnostic Markers ◽

Gene Expression Patterns

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Upregulation of Complement Factor H by SOCS-1/3–STAT4 in Lung Cancer

Cancers ◽

10.3390/cancers11040471 ◽

2019 ◽

Vol 11 (4) ◽

pp. 471 ◽

Cited By ~ 5

Author(s):

Yeon-Hee Yoon ◽

Hyeon-Ji Hwang ◽

Hye-Jin Sung ◽

Sun-Hee Heo ◽

Dong-Sun Kim ◽

...

Keyword(s):

Lung Cancer ◽

Transcription Factor ◽

Cancer Cells ◽

Expression Patterns ◽

Factor H ◽

Complement Factor H ◽

Lung Cancer Cells ◽

Luciferase Reporter ◽

Complement Factor ◽

Low Level

Complement factor H (CFH) is a fluid phase regulator of complement proteins and functions to prevent complement attack and immune surveillance. CFH is known to inactivate therapeutic antibody-dependent complement-mediated cellular cytotoxicity. We found that CFH was highly expressed in human lung cancer cells and tissues. To investigate mechanisms of CFH upregulation, we searched for a CFH transcription factor and its regulatory factors. First, signal transducer and activator of transcription 4 (STAT4) expression patterns coincided with CFH expression patterns in lung cancer tissues. Knockdown of STAT4 led to decreased CFH secretion from lung cancer cells. STAT4 bound directly to the CFH promoter, as demonstrated by luciferase reporter assay, electrophoretic mobility shift assay (EMSA), and chromatin immunoprecipitation (ChIP) assay, suggesting that STAT4 is a transcription factor for CFH. In addition, a low level of suppressors of cytokine signaling (SOCS)-1/3, a Janus kinase (JAK) inhibitor, was observed in lung cancer cells and its transfection decreased CFH protein levels and promoter activity. Unexpectedly, the low level of SOCS-1/3 was not due to epigenetic silencing. Instead, differential methylation was found on the regulatory region of STAT4 between normal and lung cancer cells. In conclusion, our results demonstrated that CFH is upregulated by constitutive activation of STAT4, which is accounted for by SOCS silencing in lung cancer cells.

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