Prognostic Value of Germline Copy Number Variants and Environmental Exposures in Non-small Cell Lung Cancer
Prognostic Value of Germline Copy Number Variants and Environmental Exposures in Non-small Cell Lung Cancer
Germline copy number variant (gCNV) has been studied as a genetic determinant for prognosis of several types of cancer, but little is known about how it affects non-small cell lung cancer (NSCLC) prognosis. We aimed to develop a prognostic nomogram for NSCLC based on gCNVs. Promising gCNVs that are associated with overall survival (OS) of NSCLC were sorted by analyzing the TCGA data and were validated in a small Chinese population. Then the successfully verified gCNVs were determined in a training cohort (n = 570) to develop a prognostic nomogram, and in a validation cohort (n = 465) to validate the nomogram. Thirty-five OS-related gCNVs were sorted and were reduced to 15 predictors by the Lasso regression analysis. Of them, only CNVR395.1 and CNVR2239.1 were confirmed to be associated with OS of NSCLC in the Chinese population. High polygenic risk score (PRS), which was calculated by the hazard effects of CNVR395.1 and CNVR2239.1, exerted a significantly higher death rate in the training cohort (HR = 1.41, 95%CI: 1.16–1.74) and validation cohort (HR = 1.42, 95%CI: 1.13–1.77) than low PRS. The nomogram incorporating PRS and surrounding factors, achieved admissible concordance indexes of 0.678 (95%CI: 0.664–0.693) and 0.686 (95%CI: 0.670–0.702) in predicting OS in the training and validation cohorts, respectively, and had well-fitted calibration curves. Moreover, an interaction between PRS and asbestos exposure was observed on affecting OS (Pinteraction = 0.042). Our analysis developed a nomogram that achieved an admissible prediction of NSCLC survival, which would be beneficial to the personalized intervention of NSCLC.
- University of Otago
- University of Otago
- University of Otago
- State Key Laboratory of Respiratory Disease China (People's Republic of)
- First Affiliated Hospital of Guangzhou Medical University China (People's Republic of)
germline copy number variant, nomogram, overall survival, Genetics, QH426-470, non-small cell lung cancer, gene-environment interaction
germline copy number variant, nomogram, overall survival, Genetics, QH426-470, non-small cell lung cancer, gene-environment interaction
5 Research products, page 1 of 1
- 2021IsAmongTopNSimilarDocuments
- 2018IsAmongTopNSimilarDocuments
- 2019IsAmongTopNSimilarDocuments
- 2014IsAmongTopNSimilarDocuments
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).0 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Average influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Average
