An epithelial-to-mesenchymal transition induced extracellular vesicle prognostic signature in non-small cell lung cancer

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Abstract

Despite significant therapeutic advances, lung cancer remains the leading cause of cancer-related death worldwide ¹. Non-small cell lung cancer (NSCLC) patients have a very poor overall five-year survival rate of only 10–20%. Currently, TNM staging is the gold standard for predicting overall survival and selecting optimal initial treatment options for NSCLC patients, including those with curable stages of disease. However, many patients with locoregionally-confined NSCLC relapse and die despite curative-intent interventions, indicating a need for intensified, individualised therapies. Epithelial-to-mesenchymal transition (EMT), the phenotypic depolarisation of epithelial cells to elongated, mesenchymal cells, is associated with metastatic and treatment-refractive cancer. We demonstrate here that EMT-induced protein changes in small extracellular vesicles are detectable in NSCLC patients and have prognostic significance. Overall, this work describes a novel prognostic biomarker signature that identifies potentially-curable NSCLC patients at risk of developing metastatic NSCLC, thereby enabling implementation of personalised treatment decisions.

Abstract

EMT-induced protein changes in small extracellular vesicles are detectable in NSCLC patients and have prognostic significance.

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Most cited references 47

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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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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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Global cancer statistics, 2012.

Lindsey A Torre, Freddie Bray, Rebecca Siegel … (2015)

Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests. © 2015 American Cancer Society.

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Author and article information

Contributors

Andreas Möller:

ORCID: http://orcid.org/0000-0002-8618-6998

andreas.moller@qimrberghofer.edu.au

Journal

Journal ID (nlm-ta): Commun Biol

Journal ID (iso-abbrev): Commun Biol

Title: Communications Biology

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2399-3642

Publication date (Electronic): 18 January 2023

Publication date PMC-release: 18 January 2023

Publication date Collection: 2023

Volume: 6

Electronic Location Identifier: 68

Affiliations

[1 ]GRID grid.1049.c, ISNI 0000 0001 2294 1395, Tumour Microenvironment Laboratory, , QIMR Berghofer Medical Research Institute, ; Herston, QLD 4006 Australia

[2 ]GRID grid.1003.2, ISNI 0000 0000 9320 7537, Faculty of Medicine, , University of Queensland, ; Brisbane, QLD 4072 Australia

[3 ]GRID grid.1024.7, ISNI 0000000089150953, School of Biomedical Sciences, Faculty of Health, , Queensland University of Technology, ; Brisbane, QLD 4001 Australia

[4 ]GRID grid.1049.c, ISNI 0000 0001 2294 1395, Protein Discovery Centre, , QIMR Berghofer Medical Research Institute, ; Herston, QLD 4006 Australia

[5 ]GRID grid.1055.1, ISNI 0000000403978434, Department of Radiation Oncology, , Peter MacCallum Cancer Centre, ; Melbourne, VIC 3000 Australia

[6 ]GRID grid.1003.2, ISNI 0000 0000 9320 7537, UQ Thoracic Research Centre, , The University of Queensland, ; Brisbane, QLD 4072 Australia

[7 ]GRID grid.415184.d, ISNI 0000 0004 0614 0266, The Prince Charles Hospital, ; Brisbane, QLD 4032 Australia

[8 ]GRID grid.1008.9, ISNI 0000 0001 2179 088X, Sir Peter MacCallum Department of Oncology, , The University of Melbourne, ; Melbourne, VIC 3000 Australia

[9 ]GRID grid.1049.c, ISNI 0000 0001 2294 1395, Oncogenomics Laboratory, , QIMR Berghofer Medical Research Institute, ; Herston, QLD 4006 Australia

[10 ]Swiss Medical Network, Genolier, VD 1272 Switzerland

[11 ]GRID grid.10784.3a, ISNI 0000 0004 1937 0482, Present Address: Department of Otorhinolaryngology, , Chinese University of Hong Kong, ; Shatin, Hong Kong

Author information

Kekoolani S. Visan http://orcid.org/0000-0002-8393-4209

Li-Ying Wu http://orcid.org/0000-0002-1509-9440

Andreas Möller http://orcid.org/0000-0002-8618-6998

Article

Publisher ID: 4350

DOI: 10.1038/s42003-022-04350-4

PMC ID: 9849257

PubMed ID: 36653467

SO-VID: b7bb7115-907a-40ee-af8a-76b6485f819e

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 31 March 2022

Date accepted : 8 December 2022

Funding

Funded by: FundRef https://doi.org/10.13039/501100000925, Department of Health | National Health and Medical Research Council (NHMRC);

Award ID: 1185907

Award ID: 1164020

Award ID: 1068510

Award Recipient : Andreas Möller

Funded by: FundRef https://doi.org/10.13039/501100001043, Cass Foundation;

Award ID: SM12/4249

Award Recipient : Andreas Möller

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Keywords: prognostic markers,non-small-cell lung cancer

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Keywords: prognostic markers, non-small-cell lung cancer

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An epithelial-to-mesenchymal transition induced extracellular vesicle prognostic signature in non-small cell lung cancer

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Abstract

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Bacterial extracellular vesicles

Most cited references 47

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

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

Global cancer statistics, 2012.

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Cited by 4

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