Genetic Variations in the Transforming Growth Factor-β1 Pathway May Improve Predictive Power for Overall Survival in Non-small Cell Lung Cancer
Kong, Feng-Ming Spring
JournalFrontiers in Oncology
PublisherFrontiers Media S.A.
MetadataShow full item record
AbstractPurpose: Transforming growth factor-β1 (TGF-β1), a known immune suppressor, plays an important role in tumor progression and overall survival (OS) in many types of cancers. We hypothesized that genetic variations of single nucleotide polymorphisms (SNPs) in the TGF-β1 pathway can predict survival in patients with non-small cell lung cancer (NSCLC) after radiation therapy. Materials and Methods: Fourteen functional SNPs in the TGF-β1 pathway were measured in 166 patients with NSCLC enrolled in a multi-center clinical trial. Clinical factors, including age, gender, ethnicity, smoking status, stage group, histology, Karnofsky Performance Status, equivalent dose at 2 Gy fractions (EQD2), and the use of chemotherapy, were first tested under the univariate Cox's proportional hazards model. All significant clinical predictors were combined as a group of predictors named "Clinical." The significant SNPs under the Cox proportional hazards model were combined as a group of predictors named "SNP." The predictive powers of models using Clinical and Clinical + SNP were compared with the cross-validation concordance index (C-index) of random forest models. Results: Age, gender, stage group, smoking, histology, and EQD2 were identified as significant clinical predictors: Clinical. Among 14 SNPs, BMP2:rs235756 (HR = 0.63; 95% CI:0.42-0.93; p = 0.022), SMAD9:rs7333607 (HR = 2.79; 95% CI 1.22-6.41; p = 0.015), SMAD3:rs12102171 (HR = 0.68; 95% CI: 0.46-1.00; p = 0.050), and SMAD4: rs12456284 (HR = 0.63; 95% CI: 0.43-0.92; p = 0.016) were identified as powerful predictors of SNP. After adding SNP, the C-index of the model increased from 84.1 to 87.6% at 24 months and from 79.4 to 84.4% at 36 months. Conclusion: Genetic variations in the TGF-β1 pathway have the potential to improve the prediction accuracy for OS in patients with NSCLC.
Rights/TermsCopyright © 2021 Zhang, Wang, Pi, Bi, DesRosiers, Kong, Cheng, Yang, Lautenschlaeger, Jolly, Jin and Kong.
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/16254
- Genetic variations in the transforming growth factor-beta pathway as predictors of survival in advanced non-small cell lung cancer.
- Authors: Lin M, Stewart DJ, Spitz MR, Hildebrandt MA, Lu C, Lin J, Gu J, Huang M, Lippman SM, Wu X
- Issue date: 2011 Jul
- Nomograms incorporating genetic variants in BMP/Smad4/Hamp pathway to predict disease outcomes after definitive radiotherapy for non-small cell lung cancer.
- Authors: Yang J, Xu T, Gomez DR, Yuan X, Nguyen QN, Jeter M, Song Y, Komaki R, Hu Y, Hahn SM, Liao Z
- Issue date: 2018 Jun
- Changes of circulating transforming growth factor-beta1 level during radiation therapy are correlated with the prognosis of locally advanced non-small cell lung cancer.
- Authors: Zhao L, Ji W, Zhang L, Ou G, Feng Q, Zhou Z, Lei M, Yang W, Wang L
- Issue date: 2010 Apr
- SNPs in the transforming growth factor-β pathway as predictors of outcome in advanced lung adenocarcinoma with EGFR mutations treated with gefitinib.
- Authors: Zhang L, Li QX, Wu HL, Lu X, Yang M, Yu SY, Yuan XL
- Issue date: 2014 Aug
- Elevation of plasma TGF-beta1 during radiation therapy predicts radiation-induced lung toxicity in patients with non-small-cell lung cancer: a combined analysis from Beijing and Michigan.
- Authors: Zhao L, Wang L, Ji W, Wang X, Zhu X, Hayman JA, Kalemkerian GP, Yang W, Brenner D, Lawrence TS, Kong FM
- Issue date: 2009 Aug 1