Transcriptomic analysis reveals a tissue-specific loss of identity during ageing and cancer

Gabriel Arantes Dos Santos; Kasit Chatsirisupachai; Roberto A Avelar; João Pedro de Magalhães

doi:10.1186/s12864-023-09756-w

Transcriptomic analysis reveals a tissue-specific loss of identity during ageing and cancer

Gabriel Arantes Dos Santos, Kasit Chatsirisupachai, Roberto A Avelar, João Pedro de Magalhães^*

^*Corresponding author for this work

Inflammation and Ageing

Research output: Contribution to journal › Article › peer-review

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Abstract

INTRODUCTION: Understanding changes in cell identity in cancer and ageing is of great importance. In this work, we analyzed how gene expression changes in human tissues are associated with tissue specificity during cancer and ageing using transcriptome data from TCGA and GTEx.

RESULTS: We found significant downregulation of tissue-specific genes during ageing in 40% of the tissues analyzed, which suggests loss of tissue identity with age. For most cancer types, we have noted a consistent pattern of downregulation in genes that are specific to the tissue from which the tumor originated. Moreover, we observed in cancer an activation of genes not usually expressed in the tissue of origin as well as an upregulation of genes specific to other tissues. These patterns in cancer were associated with patient survival. The age of the patient, however, did not influence these patterns.

CONCLUSION: We identified loss of cellular identity in 40% of the tissues analysed during human ageing, and a clear pattern in cancer, where during tumorigenesis cells express genes specific to other organs while suppressing the expression of genes from their original tissue. The loss of cellular identity observed in cancer is associated with prognosis and is not influenced by age, suggesting that it is a crucial stage in carcinogenesis.

Original language	English
Article number	644
Number of pages	13
Journal	BMC Genomics
Volume	24
Issue number	1
DOIs	https://doi.org/10.1186/s12864-023-09756-w
Publication status	Published - 26 Oct 2023

Bibliographical note

Funding
GAS is financed by the scholarship “Bolsa de Excelência em Medicina Domingos Nelson Martins” of the Faculty of Medicine of the University of São Paulo (FMUSP). Work in our lab is supported by grants from the Wellcome Trust (208375/Z/17/Z), Longevity Impetus Grants, LongeCity and the Biotechnology and Biological Sciences Research Council (BB/R014949/1 and BB/V010123/1).

Copyright:
© 2023. The Author(s).

Keywords

Humans
Transcriptome
Aging/genetics
Neoplasms/genetics
Gene Expression Profiling
Carcinogenesis/genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1186/s12864-023-09756-wLicence: Creative Commons: Attribution (CC BY)

dosSantosGA2023Transcriptomic Final published version, 2.35 MBLicence: Creative Commons: Attribution (CC BY)

GeneFriends: A gene and transcript co-expression resource
Lourenco Rocha De Magalhaes, J. P. (Principal Investigator)
The Wellcome Trust
1/09/22 → 28/08/24
Project: Research

Cite this

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abstract = "INTRODUCTION: Understanding changes in cell identity in cancer and ageing is of great importance. In this work, we analyzed how gene expression changes in human tissues are associated with tissue specificity during cancer and ageing using transcriptome data from TCGA and GTEx.RESULTS: We found significant downregulation of tissue-specific genes during ageing in 40% of the tissues analyzed, which suggests loss of tissue identity with age. For most cancer types, we have noted a consistent pattern of downregulation in genes that are specific to the tissue from which the tumor originated. Moreover, we observed in cancer an activation of genes not usually expressed in the tissue of origin as well as an upregulation of genes specific to other tissues. These patterns in cancer were associated with patient survival. The age of the patient, however, did not influence these patterns.CONCLUSION: We identified loss of cellular identity in 40% of the tissues analysed during human ageing, and a clear pattern in cancer, where during tumorigenesis cells express genes specific to other organs while suppressing the expression of genes from their original tissue. The loss of cellular identity observed in cancer is associated with prognosis and is not influenced by age, suggesting that it is a crucial stage in carcinogenesis.",

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note = "Funding GAS is financed by the scholarship “Bolsa de Excel{\^e}ncia em Medicina Domingos Nelson Martins” of the Faculty of Medicine of the University of S{\~a}o Paulo (FMUSP). Work in our lab is supported by grants from the Wellcome Trust (208375/Z/17/Z), Longevity Impetus Grants, LongeCity and the Biotechnology and Biological Sciences Research Council (BB/R014949/1 and BB/V010123/1). Copyright: {\textcopyright} 2023. The Author(s).",

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AU - de Magalhães, João Pedro

N1 - Funding GAS is financed by the scholarship “Bolsa de Excelência em Medicina Domingos Nelson Martins” of the Faculty of Medicine of the University of São Paulo (FMUSP). Work in our lab is supported by grants from the Wellcome Trust (208375/Z/17/Z), Longevity Impetus Grants, LongeCity and the Biotechnology and Biological Sciences Research Council (BB/R014949/1 and BB/V010123/1). Copyright: © 2023. The Author(s).

PY - 2023/10/26

Y1 - 2023/10/26

N2 - INTRODUCTION: Understanding changes in cell identity in cancer and ageing is of great importance. In this work, we analyzed how gene expression changes in human tissues are associated with tissue specificity during cancer and ageing using transcriptome data from TCGA and GTEx.RESULTS: We found significant downregulation of tissue-specific genes during ageing in 40% of the tissues analyzed, which suggests loss of tissue identity with age. For most cancer types, we have noted a consistent pattern of downregulation in genes that are specific to the tissue from which the tumor originated. Moreover, we observed in cancer an activation of genes not usually expressed in the tissue of origin as well as an upregulation of genes specific to other tissues. These patterns in cancer were associated with patient survival. The age of the patient, however, did not influence these patterns.CONCLUSION: We identified loss of cellular identity in 40% of the tissues analysed during human ageing, and a clear pattern in cancer, where during tumorigenesis cells express genes specific to other organs while suppressing the expression of genes from their original tissue. The loss of cellular identity observed in cancer is associated with prognosis and is not influenced by age, suggesting that it is a crucial stage in carcinogenesis.

AB - INTRODUCTION: Understanding changes in cell identity in cancer and ageing is of great importance. In this work, we analyzed how gene expression changes in human tissues are associated with tissue specificity during cancer and ageing using transcriptome data from TCGA and GTEx.RESULTS: We found significant downregulation of tissue-specific genes during ageing in 40% of the tissues analyzed, which suggests loss of tissue identity with age. For most cancer types, we have noted a consistent pattern of downregulation in genes that are specific to the tissue from which the tumor originated. Moreover, we observed in cancer an activation of genes not usually expressed in the tissue of origin as well as an upregulation of genes specific to other tissues. These patterns in cancer were associated with patient survival. The age of the patient, however, did not influence these patterns.CONCLUSION: We identified loss of cellular identity in 40% of the tissues analysed during human ageing, and a clear pattern in cancer, where during tumorigenesis cells express genes specific to other organs while suppressing the expression of genes from their original tissue. The loss of cellular identity observed in cancer is associated with prognosis and is not influenced by age, suggesting that it is a crucial stage in carcinogenesis.

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KW - Aging/genetics

KW - Neoplasms/genetics

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Transcriptomic analysis reveals a tissue-specific loss of identity during ageing and cancer

Abstract

Bibliographical note

Keywords

UN SDGs

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Projects

GeneFriends: A gene and transcript co-expression resource

Cite this