Comprehensive analysis to identify GNG7 as a prognostic biomarker in lung adenocarcinoma correlating with immune infiltrates

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Abstract

Background: G Protein Subunit Gamma 7 (GNG7), an important regulator of cell proliferation and cell apoptosis, has been reported to be downregulated in a variety of tumors including lung adenocarcinoma (LUAD). However, the correlation between low expression of GNG7 and prognosis of LUAD as well as the immune infiltrates of LUAD remains unclear.

Methods: The samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). R software was performed for statistical analysis. GNG7 expression and its prognostic value in LUAD were assessed through statistically analyzing the data from different databases. A nomogram was constructed to predict the impact of GNG7 on prognosis. Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analyses GSEA (ssGSEA) were employed to determine the potential signal pathways and evaluated the immune cell infiltration regulated by GNG7. The prognostic significance of GNG7 expression associated with immune cell infiltration was investigated using the Tumor Immune Estimation Resource 2.0 (TIMER2.0) and the Kaplan-Meier plotter database. The UALCAN, cBio Cancer Genomics Portal (cBioPortal) and MethSurv database were used to analyze the correlation between the methylation of GNG7 and its mRNA expression as well as prognostic significance.

Results: GNG7 was demonstrated to be down-regulated in LUAD and its low expression was associated with poor prognosis. A clinical reliable prognostic-predictive model was constructed. Pathway enrichment showed that GNG7 was highly related to the B cell receptor signaling pathway. Further analysis showed that GNG7 was positively associated with B cell infiltration and low levels of B cell infiltration tended to associate with worse prognosis in patients with low GNG7 expression. Moreover, methylation analysis suggested hypermethylation may contribute to the low expression of GNG7 in LUAD.

Conclusion: Decreased expression of GNG7 at least partly caused by hypermethylation of the GNG7 promoter is closely associated with poor prognosis and tumor immune cell infiltration (especially B cells) in LUAD. These results suggest that GNG7 may be a promising prognostic biomarker and a potential immunotherapeutic target for LUAD, which provides new insights into immunotherapy for LUAD.

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Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)

This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.

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Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

Michael Love, Wolfgang Huber, Simon Anders (2014)

In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.

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Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

A. Subramanian, P. Tamayo, V. K. Mootha … (2005)

Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.

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Author and article information

Contributors

Pengju Zhang: URI : https://loop.frontiersin.org/people/1167221/overview

Journal

Journal ID (nlm-ta): Front Genet

Journal ID (iso-abbrev): Front Genet

Journal ID (publisher-id): Front. Genet.

Title: Frontiers in Genetics

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1664-8021

Publication date (Electronic): 09 September 2022

Publication date Collection: 2022

Volume: 13

Electronic Location Identifier: 984575

Affiliations

[1] ¹ Department of Biochemistry and Molecular Biology , Shandong University School of Basic Medical Sciences , Jinan, China

[2] ² Department of Radiology , Qilu Hospital of Shandong University , Jinan, China

[3] ³ Department of Gastroenterology , Affiliated Hospital of Shandong University of Traditional Chinese Medicine , Jinan, China

Author notes

Edited by: Saurav Mallik, Harvard University, United States

Reviewed by: Loveleen Gaur, Amity University, India

Soumita Seth, Aliah University, India

*Correspondence: Hua Yan, 71001643@ 123456sdutcm.edu.cn

This article was submitted to Computational Genomics, a section of the journal Frontiers in Genetics

Article

Publisher ID: 984575

DOI: 10.3389/fgene.2022.984575

PMC ID: 9500342

SO-VID: 5e719c21-c900-4d49-96ea-11088d93ee36

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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 02 July 2022

Date accepted : 08 August 2022

Funding

Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;

Comprehensive analysis to identify GNG7 as a prognostic biomarker in lung adenocarcinoma correlating with immune infiltrates

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Most cited references 53

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

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