Multi-Omics Analysis of the Effects of Smoking on Human Tumors

Comprehensive studies on cancer patients with different smoking histories, including non-smokers, former smokers, and current smokers, remain elusive. Therefore, we conducted a multi-omics analysis to explore the effect of smoking history on cancer patients. Patients with smoking history were screen...

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Main Authors: Rui Wang, Shanshan Li, Wen Wen, Jianquan Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-11-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2021.704910/full
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author Rui Wang
Shanshan Li
Wen Wen
Jianquan Zhang
author_facet Rui Wang
Shanshan Li
Wen Wen
Jianquan Zhang
author_sort Rui Wang
collection DOAJ
description Comprehensive studies on cancer patients with different smoking histories, including non-smokers, former smokers, and current smokers, remain elusive. Therefore, we conducted a multi-omics analysis to explore the effect of smoking history on cancer patients. Patients with smoking history were screened from The Cancer Genome Atlas database, and their multi-omics data and clinical information were downloaded. A total of 2,317 patients were included in this study, whereby current smokers presented the worst prognosis, followed by former smokers, while non-smokers showed the best prognosis. More importantly, smoking history was an independent prognosis factor. Patients with different smoking histories exhibited different immune content, and former smokers had the highest immune cells and tumor immune microenvironment. Smokers are under a higher incidence of genomic instability that can be reversed following smoking cessation in some changes. We also noted that smoking reduced the sensitivity of patients to chemotherapeutic drugs, whereas smoking cessation can reverse the situation. Competing endogenous RNA network revealed that mir-193b-3p, mir-301b, mir-205-5p, mir-132-3p, mir-212-3p, mir-1271-5p, and mir-137 may contribute significantly in tobacco-mediated tumor formation. We identified 11 methylation driver genes (including EIF5A2, GBP6, HGD, HS6ST1, ITGA5, NR2F2, PLS1, PPP1R18, PTHLH, SLC6A15, and YEATS2), and methylation modifications of some of these genes have not been reported to be associated with tumors. We constructed a 46-gene model that predicted overall survival with good predictive power. We next drew nomograms of each cancer type. Interestingly, calibration diagrams and concordance indexes are verified that the nomograms were highly accurate for the prognosis of patients. Meanwhile, we found that the 46-gene model has good applicability to the overall survival as well as to disease-specific survival and progression-free intervals. The results of this research provide new and valuable insights for the diagnosis, treatment, and follow-up of cancer patients with different smoking histories.
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spelling doaj.art-6a561d0b1d664063acb7df445a3eb6092022-12-21T21:34:43ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-11-01810.3389/fmolb.2021.704910704910Multi-Omics Analysis of the Effects of Smoking on Human TumorsRui Wang0Shanshan Li1Wen Wen2Jianquan Zhang3Department of Hepatobiliary Surgery, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, ChinaDepartment of Nursing, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, ChinaDepartment of Hepatobiliary Surgery, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, ChinaDepartment of Hepatobiliary Surgery, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou, ChinaComprehensive studies on cancer patients with different smoking histories, including non-smokers, former smokers, and current smokers, remain elusive. Therefore, we conducted a multi-omics analysis to explore the effect of smoking history on cancer patients. Patients with smoking history were screened from The Cancer Genome Atlas database, and their multi-omics data and clinical information were downloaded. A total of 2,317 patients were included in this study, whereby current smokers presented the worst prognosis, followed by former smokers, while non-smokers showed the best prognosis. More importantly, smoking history was an independent prognosis factor. Patients with different smoking histories exhibited different immune content, and former smokers had the highest immune cells and tumor immune microenvironment. Smokers are under a higher incidence of genomic instability that can be reversed following smoking cessation in some changes. We also noted that smoking reduced the sensitivity of patients to chemotherapeutic drugs, whereas smoking cessation can reverse the situation. Competing endogenous RNA network revealed that mir-193b-3p, mir-301b, mir-205-5p, mir-132-3p, mir-212-3p, mir-1271-5p, and mir-137 may contribute significantly in tobacco-mediated tumor formation. We identified 11 methylation driver genes (including EIF5A2, GBP6, HGD, HS6ST1, ITGA5, NR2F2, PLS1, PPP1R18, PTHLH, SLC6A15, and YEATS2), and methylation modifications of some of these genes have not been reported to be associated with tumors. We constructed a 46-gene model that predicted overall survival with good predictive power. We next drew nomograms of each cancer type. Interestingly, calibration diagrams and concordance indexes are verified that the nomograms were highly accurate for the prognosis of patients. Meanwhile, we found that the 46-gene model has good applicability to the overall survival as well as to disease-specific survival and progression-free intervals. The results of this research provide new and valuable insights for the diagnosis, treatment, and follow-up of cancer patients with different smoking histories.https://www.frontiersin.org/articles/10.3389/fmolb.2021.704910/fulltobaccocessationformer smokerscurrent smokersTCGAbioinformatics
spellingShingle Rui Wang
Shanshan Li
Wen Wen
Jianquan Zhang
Multi-Omics Analysis of the Effects of Smoking on Human Tumors
Frontiers in Molecular Biosciences
tobacco
cessation
former smokers
current smokers
TCGA
bioinformatics
title Multi-Omics Analysis of the Effects of Smoking on Human Tumors
title_full Multi-Omics Analysis of the Effects of Smoking on Human Tumors
title_fullStr Multi-Omics Analysis of the Effects of Smoking on Human Tumors
title_full_unstemmed Multi-Omics Analysis of the Effects of Smoking on Human Tumors
title_short Multi-Omics Analysis of the Effects of Smoking on Human Tumors
title_sort multi omics analysis of the effects of smoking on human tumors
topic tobacco
cessation
former smokers
current smokers
TCGA
bioinformatics
url https://www.frontiersin.org/articles/10.3389/fmolb.2021.704910/full
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AT shanshanli multiomicsanalysisoftheeffectsofsmokingonhumantumors
AT wenwen multiomicsanalysisoftheeffectsofsmokingonhumantumors
AT jianquanzhang multiomicsanalysisoftheeffectsofsmokingonhumantumors