<i>BTG2</i> Serves as a Potential Prognostic Marker and Correlates with Immune Infiltration in Lung Adenocarcinoma

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Abstract

Background

B-cell translocation gene 2 ( BTG2) has been revealed to be involved in the occurrence and development of multiple cancers. However, the role of BTG2 in lung adenocarcinoma (LUAD) is still ambiguous. Thus, this study aims to investigate the prognostic value of BTG2 and its correlation with immune infiltration in LUAD.

Methods

The expression of BTG2 in LUAD was analyzed using the TIMER and UALCAN databases. The correlations between BTG2 expression and clinicopathological factors were investigated using the UALCAN databases. The Kaplan–Meier plotter, GEPIA, and TCGA databases were employed to assess the prognostic value of BTG2. The STRING database and Cytoscape software were used to construct an interaction network and mine co-expression genes. The TISIDB database was examined for a correlation between BTG2 and driver genes in LUAD. Enrichment analysis of co-expressed genes and BTG2 was performed using the LinkedOmics database. Finally, the correlations between BTG2 and immune infiltrates were investigated using the TIMER, GEO, and TISIDB database.

Results

BTG2 was significantly downregulated in LUAD. The decreased expression of BTG2 in LUAD was significantly correlated with higher cancer stages and shorter duration of overall survival. The expressions of BTG2-related co-expression genes were associated with the prognosis in LUAD. The expression of BTG2 was closely associated with the mutations of TP53 and ROS1. Enrichment analysis revealed that BTG2 was significantly correlated with immune‐associated signaling pathways and function. In addition, the expression of BTG2 was found to be closely related to immune infiltration, multiple gene markers of immune cells, chemokines, and chemokine receptors.

Conclusion

Our findings have effectively demonstrated that BTG2 expression was downregulated in LUAD, indicating poor prognosis. Closely relating to immune cell infiltration, BTG2 may be a promising immune-related biomarker and molecular target for patients with LUAD.

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Most cited references 104

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Cytoscape: a software environment for integrated models of biomolecular interaction networks.

Paul Shannon, Andrew Markiel, Owen Ozier … (2003)

Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.

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Cancer statistics, 2018

Kimberly D Miller, Rebecca Siegel, Ahmedin Jemal (2018)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data, available through 2014, were collected by the Surveillance, Epidemiology, and End Results Program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data, available through 2015, were collected by the National Center for Health Statistics. In 2018, 1,735,350 new cancer cases and 609,640 cancer deaths are projected to occur in the United States. Over the past decade of data, the cancer incidence rate (2005-2014) was stable in women and declined by approximately 2% annually in men, while the cancer death rate (2006-2015) declined by about 1.5% annually in both men and women. The combined cancer death rate dropped continuously from 1991 to 2015 by a total of 26%, translating to approximately 2,378,600 fewer cancer deaths than would have been expected if death rates had remained at their peak. Of the 10 leading causes of death, only cancer declined from 2014 to 2015. In 2015, the cancer death rate was 14% higher in non-Hispanic blacks (NHBs) than non-Hispanic whites (NHWs) overall (death rate ratio [DRR], 1.14; 95% confidence interval [95% CI], 1.13-1.15), but the racial disparity was much larger for individuals aged <65 years (DRR, 1.31; 95% CI, 1.29-1.32) compared with those aged ≥65 years (DRR, 1.07; 95% CI, 1.06-1.09) and varied substantially by state. For example, the cancer death rate was lower in NHBs than NHWs in Massachusetts for all ages and in New York for individuals aged ≥65 years, whereas for those aged <65 years, it was 3 times higher in NHBs in the District of Columbia (DRR, 2.89; 95% CI, 2.16-3.91) and about 50% higher in Wisconsin (DRR, 1.78; 95% CI, 1.56-2.02), Kansas (DRR, 1.51; 95% CI, 1.25-1.81), Louisiana (DRR, 1.49; 95% CI, 1.38-1.60), Illinois (DRR, 1.48; 95% CI, 1.39-1.57), and California (DRR, 1.45; 95% CI, 1.38-1.54). Larger racial inequalities in young and middle-aged adults probably partly reflect less access to high-quality health care. CA Cancer J Clin 2018;68:7-30. © 2018 American Cancer Society.

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TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells.

Taiwen Li, Jingyu Fan, Binbin Wang … (2017)

Recent clinical successes of cancer immunotherapy necessitate the investigation of the interaction between malignant cells and the host immune system. However, elucidation of complex tumor-immune interactions presents major computational and experimental challenges. Here, we present Tumor Immune Estimation Resource (TIMER; cistrome.shinyapps.io/timer) to comprehensively investigate molecular characterization of tumor-immune interactions. Levels of six tumor-infiltrating immune subsets are precalculated for 10,897 tumors from 32 cancer types. TIMER provides 6 major analytic modules that allow users to interactively explore the associations between immune infiltrates and a wide spectrum of factors, including gene expression, clinical outcomes, somatic mutations, and somatic copy number alterations. TIMER provides a user-friendly web interface for dynamic analysis and visualization of these associations, which will be of broad utilities to cancer researchers. Cancer Res; 77(21); e108-10. ©2017 AACR.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Gen Med

Journal ID (iso-abbrev): Int J Gen Med

Journal ID (publisher-id): ijgm

Title: International Journal of General Medicine

Publisher: Dove

ISSN (Electronic): 1178-7074

Publication date (Electronic): 08 March 2022

Publication date Collection: 2022

Volume: 15

Pages: 2727-2745

Affiliations

[1 ]Department of Radiation Oncology, Guangxi Medical University Cancer Hospital , Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China

[2 ]Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine , Guangzhou, 510060, Guangdong, People’s Republic of China

[3 ]Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital , Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China

[4 ]Department of Breast-Thoracic Tumor Surgery, The First Affiliated Hospital of Hainan Medical University , Haikou, 570102, Hainan, People’s Republic of China

Author notes

Correspondence: Shi Xiong Liang; Wei Jiang, Email shixliang@vip.sina.com; weicy2016@163.com

[*]

These authors contributed equally to this work

Article

Publisher ID: 340565

DOI: 10.2147/IJGM.S340565

PMC ID: 8922043

SO-VID: 3c49abfe-2489-43ab-a1fc-5665977cd3e1

License:

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 16 October 2021

Date accepted : 26 January 2022

Page count

Figures: 10, Tables: 8, References: 104, Pages: 19

Funding

Funded by: Key Program of Science and Technology of Guangxi, China;

Funded by: Guangxi Natural Science Foundation, open-funder-registry 10.13039/501100004607;

Funded by: Beijing Xisike Clinical Oncology Research Foundation;

The work was funded by the Key Program of Science and Technology of Guangxi, China (GuikeAB20159024), Guangxi Natural Science Foundation (2018GXNSFAA281057), and Beijing Xisike Clinical Oncology Research Foundation (Y-2019AZQN-04532).

BTG2 Serves as a Potential Prognostic Marker and Correlates with Immune Infiltration in Lung Adenocarcinoma

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Most cited references 104

Cytoscape: a software environment for integrated models of biomolecular interaction networks.

Cancer statistics, 2018

TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells.

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