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Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer

Cancer remains a formidable challenge in medicine due to its propensity for recurrence and metastasis, which can result in unfavorable treatment outcomes. This challenge is particularly acute for early-stage patients, who may experience recurrence and metastasis without timely detection. Here, we fi...

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Autores principales: He, Dan-ni, Wang, Na, Wen, Xiao-Ling, Li, Xu-Hua, Guo, Yu, Fu, Shu-heng, Xiong, Fei-fan, Wu, Zhe-yu, Zhu, Xu, Gao, Xiao-ling, Wang, Zhen-zhen, Wang, Hong-jiu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157260/
https://www.ncbi.nlm.nih.gov/pubmed/37152984
http://dx.doi.org/10.3389/fgene.2023.1061364
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author He, Dan-ni
Wang, Na
Wen, Xiao-Ling
Li, Xu-Hua
Guo, Yu
Fu, Shu-heng
Xiong, Fei-fan
Wu, Zhe-yu
Zhu, Xu
Gao, Xiao-ling
Wang, Zhen-zhen
Wang, Hong-jiu
author_facet He, Dan-ni
Wang, Na
Wen, Xiao-Ling
Li, Xu-Hua
Guo, Yu
Fu, Shu-heng
Xiong, Fei-fan
Wu, Zhe-yu
Zhu, Xu
Gao, Xiao-ling
Wang, Zhen-zhen
Wang, Hong-jiu
author_sort He, Dan-ni
collection PubMed
description Cancer remains a formidable challenge in medicine due to its propensity for recurrence and metastasis, which can result in unfavorable treatment outcomes. This challenge is particularly acute for early-stage patients, who may experience recurrence and metastasis without timely detection. Here, we first analyzed the differences in clinical characteristics among the primary tumor, recurrent tumor, and metastatic tumor in different stages of cancer, which may be caused by the molecular level. Moreover, the importance of predicting early cancer recurrence and metastasis is emphasized by survival analyses. Next, we used a multi-omics approach to identify key molecular changes associated with early cancer recurrence and metastasis and discovered that early metastasis in cancer demonstrated a high degree of genomic and cellular heterogeneity. We performed statistical comparisons for each level of omics data including gene expression, mutation, copy number variation, immune cell infiltration, and cell status. Then, various analytical techniques, such as proportional hazard model and Fisher’s exact test, were used to identify specific genes or immune characteristics associated with early cancer recurrence and metastasis. For example, we observed that the overexpression of BPIFB1 and high initial B-cell infiltration levels are linked to early cancer recurrence, while the overexpression or amplification of ANKRD22 and LIPM, mutation of IGHA1 and MUC16, high fibroblast infiltration level, M1 polarization of macrophages, cellular status of DNA repair are all linked to early cancer metastasis. These findings have led us to construct classifiers, and the average area under the curve (AUC) of these classifiers was greater than 0.75 in The Cancer Genome Atlas (TCGA) cancer patients, confirming that the features we identified could be biomarkers for predicting recurrence and metastasis of early cancer. Finally, we identified specific early sensitive targets for targeted therapy and immune checkpoint inhibitor therapy. Once the biomarkers we identified changed, treatment-sensitive targets can be treated accordingly. Our study has comprehensively characterized the multi-omics characteristics and identified a panel of biomarkers of early cancer recurrence and metastasis. Overall, it provides a valuable resource for cancer recurrence and metastasis research and improves our understanding of the underlying mechanisms driving early cancer recurrence and metastasis.
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spelling pubmed-101572602023-05-05 Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer He, Dan-ni Wang, Na Wen, Xiao-Ling Li, Xu-Hua Guo, Yu Fu, Shu-heng Xiong, Fei-fan Wu, Zhe-yu Zhu, Xu Gao, Xiao-ling Wang, Zhen-zhen Wang, Hong-jiu Front Genet Genetics Cancer remains a formidable challenge in medicine due to its propensity for recurrence and metastasis, which can result in unfavorable treatment outcomes. This challenge is particularly acute for early-stage patients, who may experience recurrence and metastasis without timely detection. Here, we first analyzed the differences in clinical characteristics among the primary tumor, recurrent tumor, and metastatic tumor in different stages of cancer, which may be caused by the molecular level. Moreover, the importance of predicting early cancer recurrence and metastasis is emphasized by survival analyses. Next, we used a multi-omics approach to identify key molecular changes associated with early cancer recurrence and metastasis and discovered that early metastasis in cancer demonstrated a high degree of genomic and cellular heterogeneity. We performed statistical comparisons for each level of omics data including gene expression, mutation, copy number variation, immune cell infiltration, and cell status. Then, various analytical techniques, such as proportional hazard model and Fisher’s exact test, were used to identify specific genes or immune characteristics associated with early cancer recurrence and metastasis. For example, we observed that the overexpression of BPIFB1 and high initial B-cell infiltration levels are linked to early cancer recurrence, while the overexpression or amplification of ANKRD22 and LIPM, mutation of IGHA1 and MUC16, high fibroblast infiltration level, M1 polarization of macrophages, cellular status of DNA repair are all linked to early cancer metastasis. These findings have led us to construct classifiers, and the average area under the curve (AUC) of these classifiers was greater than 0.75 in The Cancer Genome Atlas (TCGA) cancer patients, confirming that the features we identified could be biomarkers for predicting recurrence and metastasis of early cancer. Finally, we identified specific early sensitive targets for targeted therapy and immune checkpoint inhibitor therapy. Once the biomarkers we identified changed, treatment-sensitive targets can be treated accordingly. Our study has comprehensively characterized the multi-omics characteristics and identified a panel of biomarkers of early cancer recurrence and metastasis. Overall, it provides a valuable resource for cancer recurrence and metastasis research and improves our understanding of the underlying mechanisms driving early cancer recurrence and metastasis. Frontiers Media S.A. 2023-04-20 /pmc/articles/PMC10157260/ /pubmed/37152984 http://dx.doi.org/10.3389/fgene.2023.1061364 Text en Copyright © 2023 He, Wang, Wen, Li, Guo, Fu, Xiong, Wu, Zhu, Gao, Wang and Wang. 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
He, Dan-ni
Wang, Na
Wen, Xiao-Ling
Li, Xu-Hua
Guo, Yu
Fu, Shu-heng
Xiong, Fei-fan
Wu, Zhe-yu
Zhu, Xu
Gao, Xiao-ling
Wang, Zhen-zhen
Wang, Hong-jiu
Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer
title Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer
title_full Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer
title_fullStr Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer
title_full_unstemmed Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer
title_short Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer
title_sort multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10157260/
https://www.ncbi.nlm.nih.gov/pubmed/37152984
http://dx.doi.org/10.3389/fgene.2023.1061364
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