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Construction and Clinical Translation of Causal Pan-Cancer Gene Score Across Cancer Types
Pan-cancer strategy, an integrative analysis of different cancer types, can be used to explain oncogenesis and identify biomarkers using a larger statistical power and robustness. Fine-mapping defines the casual loci, whereas genome-wide association studies (GWASs) typically identify thousands of ca...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733729/ https://www.ncbi.nlm.nih.gov/pubmed/35003220 http://dx.doi.org/10.3389/fgene.2021.784775 |
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author | Tao, Shiyue Ye, Xiangyu Pan, Lulu Fu, Minghan Huang, Peng Peng, Zhihang Yang, Sheng |
author_facet | Tao, Shiyue Ye, Xiangyu Pan, Lulu Fu, Minghan Huang, Peng Peng, Zhihang Yang, Sheng |
author_sort | Tao, Shiyue |
collection | PubMed |
description | Pan-cancer strategy, an integrative analysis of different cancer types, can be used to explain oncogenesis and identify biomarkers using a larger statistical power and robustness. Fine-mapping defines the casual loci, whereas genome-wide association studies (GWASs) typically identify thousands of cancer-related loci and not necessarily have a fine-mapping component. In this study, we develop a novel strategy to identify the causal loci using a pan-cancer and fine-mapping assumption, constructing the CAusal Pan-cancER gene (CAPER) score and validating its performance using internal and external validation on 1,287 individuals and 985 cell lines. Summary statistics of 15 cancer types were used to define 54 causal loci in 15 potential genes. Using the Cancer Genome Atlas (TCGA) training set, we constructed the CAPER score and divided cancer patients into two groups. Using the three validation sets, we found that 19 cancer-related variables were statistically significant between the two CAPER score groups and that 81 drugs had significantly different drug sensitivity between the two CAPER score groups. We hope that our strategies for selecting causal genes and for constructing CAPER score would provide valuable clues for guiding the management of different types of cancers. |
format | Online Article Text |
id | pubmed-8733729 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87337292022-01-07 Construction and Clinical Translation of Causal Pan-Cancer Gene Score Across Cancer Types Tao, Shiyue Ye, Xiangyu Pan, Lulu Fu, Minghan Huang, Peng Peng, Zhihang Yang, Sheng Front Genet Genetics Pan-cancer strategy, an integrative analysis of different cancer types, can be used to explain oncogenesis and identify biomarkers using a larger statistical power and robustness. Fine-mapping defines the casual loci, whereas genome-wide association studies (GWASs) typically identify thousands of cancer-related loci and not necessarily have a fine-mapping component. In this study, we develop a novel strategy to identify the causal loci using a pan-cancer and fine-mapping assumption, constructing the CAusal Pan-cancER gene (CAPER) score and validating its performance using internal and external validation on 1,287 individuals and 985 cell lines. Summary statistics of 15 cancer types were used to define 54 causal loci in 15 potential genes. Using the Cancer Genome Atlas (TCGA) training set, we constructed the CAPER score and divided cancer patients into two groups. Using the three validation sets, we found that 19 cancer-related variables were statistically significant between the two CAPER score groups and that 81 drugs had significantly different drug sensitivity between the two CAPER score groups. We hope that our strategies for selecting causal genes and for constructing CAPER score would provide valuable clues for guiding the management of different types of cancers. Frontiers Media S.A. 2021-12-23 /pmc/articles/PMC8733729/ /pubmed/35003220 http://dx.doi.org/10.3389/fgene.2021.784775 Text en Copyright © 2021 Tao, Ye, Pan, Fu, Huang, Peng and Yang. https://creativecommons.org/licenses/by/4.0/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. |
spellingShingle | Genetics Tao, Shiyue Ye, Xiangyu Pan, Lulu Fu, Minghan Huang, Peng Peng, Zhihang Yang, Sheng Construction and Clinical Translation of Causal Pan-Cancer Gene Score Across Cancer Types |
title | Construction and Clinical Translation of Causal Pan-Cancer Gene Score Across Cancer Types |
title_full | Construction and Clinical Translation of Causal Pan-Cancer Gene Score Across Cancer Types |
title_fullStr | Construction and Clinical Translation of Causal Pan-Cancer Gene Score Across Cancer Types |
title_full_unstemmed | Construction and Clinical Translation of Causal Pan-Cancer Gene Score Across Cancer Types |
title_short | Construction and Clinical Translation of Causal Pan-Cancer Gene Score Across Cancer Types |
title_sort | construction and clinical translation of causal pan-cancer gene score across cancer types |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733729/ https://www.ncbi.nlm.nih.gov/pubmed/35003220 http://dx.doi.org/10.3389/fgene.2021.784775 |
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