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Pan-cancer application of a lung-adenocarcinoma-derived gene-expression-based prognostic predictor

Nacer, Deborah F. LU orcid ; Liljedahl, Helena LU ; Karlsson, Anna F LU ; Lindgren, David LU and Staaf, Johan LU orcid (2021) In Briefings in Bioinformatics 22(6).
Abstract
Gene-expression profiling can be used to classify human tumors into molecular subtypes or risk groups, representing potential future clinical tools for treatment prediction and prognostication. However, it is less well-known how prognostic gene signatures derived in one malignancy perform in a pan-cancer context. In this study, a gene-rule-based single sample predictor (SSP) called classifier for lung adenocarcinoma molecular subtypes (CLAMS) associated with proliferation was tested in almost 15 000 samples from 32 cancer types to classify samples into better or worse prognosis. Of the 14 malignancies that presented both CLAMS classes in sufficient numbers, survival outcomes were significantly different for breast, brain, kidney and liver... (More)
Gene-expression profiling can be used to classify human tumors into molecular subtypes or risk groups, representing potential future clinical tools for treatment prediction and prognostication. However, it is less well-known how prognostic gene signatures derived in one malignancy perform in a pan-cancer context. In this study, a gene-rule-based single sample predictor (SSP) called classifier for lung adenocarcinoma molecular subtypes (CLAMS) associated with proliferation was tested in almost 15 000 samples from 32 cancer types to classify samples into better or worse prognosis. Of the 14 malignancies that presented both CLAMS classes in sufficient numbers, survival outcomes were significantly different for breast, brain, kidney and liver cancer. Patients with samples classified as better prognosis by CLAMS were generally of lower tumor grade and disease stage, and had improved prognosis according to other type-specific classifications (e.g. PAM50 for breast cancer). In all, 99.1% of non-lung cancer cases classified as better outcome by CLAMS were comprised within the range of proliferation scores of lung adenocarcinoma cases with a predicted better prognosis by CLAMS. This finding demonstrates the potential of tuning SSPs to identify specific levels of for instance tumor proliferation or other transcriptional programs through predictor training. Together, pan-cancer studies such as this may take us one step closer to understanding how gene-expression-based SSPs act, which gene-expression programs might be important in different malignancies, and how to derive tools useful for prognostication that are efficient across organs. (Less)
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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Briefings in Bioinformatics
volume
22
issue
6
article number
bbab154
publisher
Oxford University Press
external identifiers
  • pmid:33971670
  • pmid:33971670
  • scopus:85121951881
ISSN
1477-4054
DOI
10.1093/bib/bbab154
language
English
LU publication?
yes
id
a71fe5c7-70f9-4c18-9d9d-18fa9851cc48
date added to LUP
2021-06-02 17:30:48
date last changed
2024-05-21 04:03:25
@article{a71fe5c7-70f9-4c18-9d9d-18fa9851cc48,
  abstract     = {{Gene-expression profiling can be used to classify human tumors into molecular subtypes or risk groups, representing potential future clinical tools for treatment prediction and prognostication. However, it is less well-known how prognostic gene signatures derived in one malignancy perform in a pan-cancer context. In this study, a gene-rule-based single sample predictor (SSP) called classifier for lung adenocarcinoma molecular subtypes (CLAMS) associated with proliferation was tested in almost 15 000 samples from 32 cancer types to classify samples into better or worse prognosis. Of the 14 malignancies that presented both CLAMS classes in sufficient numbers, survival outcomes were significantly different for breast, brain, kidney and liver cancer. Patients with samples classified as better prognosis by CLAMS were generally of lower tumor grade and disease stage, and had improved prognosis according to other type-specific classifications (e.g. PAM50 for breast cancer). In all, 99.1% of non-lung cancer cases classified as better outcome by CLAMS were comprised within the range of proliferation scores of lung adenocarcinoma cases with a predicted better prognosis by CLAMS. This finding demonstrates the potential of tuning SSPs to identify specific levels of for instance tumor proliferation or other transcriptional programs through predictor training. Together, pan-cancer studies such as this may take us one step closer to understanding how gene-expression-based SSPs act, which gene-expression programs might be important in different malignancies, and how to derive tools useful for prognostication that are efficient across organs.}},
  author       = {{Nacer, Deborah F. and Liljedahl, Helena and Karlsson, Anna F and Lindgren, David and Staaf, Johan}},
  issn         = {{1477-4054}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{Oxford University Press}},
  series       = {{Briefings in Bioinformatics}},
  title        = {{Pan-cancer application of a lung-adenocarcinoma-derived gene-expression-based prognostic predictor}},
  url          = {{http://dx.doi.org/10.1093/bib/bbab154}},
  doi          = {{10.1093/bib/bbab154}},
  volume       = {{22}},
  year         = {{2021}},
}