The benefits of smoking cessation on survival in cancer patients by integrative analysis of multi-omics data
The benefits of smoking cessation on survival in cancer patients by integrative analysis of multi-omics data
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通过多组学数据综合分析戒烟对癌症患者生存的益处
DOI：
10.1002/1878-0261.12755
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发表时间：
2020-07-11
影响因子：
6.6
通讯作者：
Liang, Geyu
中科院分区：
文献类型：
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作者：
Yang, Sheng;Liu, Tong;Liang, Geyu
很少有研究调查癌症患者诊断时的吸烟状况（包括既往吸烟者）与总生存率之间的关系。我们的目的是评估从癌症基因组图谱（TCGA）数据库获得的癌症患者吸烟者队列中戒烟对癌症预后的益处。使用多变量校正的考克斯回归分析计算风险比（HR），以评价癌症诊断时吸烟行为（戒烟者vs.当前吸烟者）与总生存期的相关性。根据我们的分析，戒烟是肺鳞状细胞癌（LUSC）总生存期的独立保护因素（HR = 0.67，95%CI = 0.48-0.94）。对改造和当前吸烟者的多组分数据的综合分析确定了总共85个受不同遗传和表观遗传调控模式影响的差异表达基因（DEG），这些基因可能代表吸烟者的癌症驱动因素。此外，我们提供了一个吸烟相关基因表达特征，它可以以高功效评估对预后的真实影响（HR = 1.70，95%CI = 1.19-2.43，AUC = 0.65，0.67和0.70，分别用于2年，3年和5年生存期）。这一特征也适用于其他与吸烟相关的癌症，包括膀胱尿路上皮癌（HR = 1.70，95% CI = 1.01-2.88），宫颈癌（HR = 5.69，95% CI = 1.37-23.69），头颈部鳞状细胞癌（HR = 1.97，95% CI = 1.41-2.76）、肺腺癌（HR = 1.73，95% CI = 1.16-2.57）和胰腺癌（HR = 4.28，95% CI = 1.47-12.47）。总之，这项研究表明，在诊断时戒烟可以降低癌症患者的死亡风险。我们还提供了一个吸烟相关的基因表达特征，以评估吸烟对生存的影响。最后，我们建议戒烟可以成为癌症治疗的一部分，以提高癌症患者的生存率。
Few studies have examined the association between smoking status (including former smokers) at diagnosis and overall survival among cancer patients. We aimed to assess the benefits of quitting smoking on cancer prognosis in cohorts of cancer patient smokers obtained from the Cancer Genome Atlas (TCGA) database. Hazard ratios (HR) were calculated to evaluate smoking behavior at cancer diagnosis (reformed smokers vs. current smokers) in association with overall survival using multivariate-adjusted Cox regressions analysis. According to our analyses, quitting smoking was the independent protective factor for overall survival in lung squamous cell carcinoma (LUSC) (HR = 0.67, 95% CI = 0.48-0.94). Comprehensive analysis of multicomponent data across reformed and current smokers identified a total of 85 differential expressed genes (DEGs) affected by different modes of genetic and epigenetic regulation, potentially representing cancer drivers in smokers. Moreover, we provided a smoking-associated gene expression signature, which could evaluate the true effect on prognosis with high power (HR = 1.70, 95% CI = 1.19-2.43, AUC = 0.65, 0.67, and 0.70 for 2-, 3-, and 5-year survival, respectively). This signature was also applicable in other smoking-related cancers, including bladder urothelial carcinoma (HR = 1.70, 95% CI = 1.01-2.88), cervical carcinoma (HR = 5.69, 95% CI = 1.37-23.69), head and neck squamous cell carcinoma (HR = 1.97, 95% CI = 1.41-2.76), lung adenocarcinoma (HR = 1.73, 95% CI = 1.16-2.57), and pancreatic adenocarcinoma (HR = 4.28, 95% CI = 1.47-12.47). In conclusion, this study demonstrates that quitting smoking at diagnosis decreases risk of death in cancer patients. We also provide a smoking-associated gene expression signature to evaluate the effect of smoking on survival. Lastly, we suggest that smoking cessation could comprise a part of cancer treatment to improve survival rates of cancer patients.