Pathway-based gene signatures predicting clinical outcome of lung adenocarcinoma - PubMed (original) (raw)

Pathway-based gene signatures predicting clinical outcome of lung adenocarcinoma

Ya-Hsuan Chang et al. Sci Rep. 2015.

Abstract

Lung adenocarcinoma is often diagnosed at an advanced stage with poor prognosis. Patients with different clinical outcomes may have similar clinico-pathological characteristics. The results of previous studies for biomarkers for lung adenocarcinoma have generally been inconsistent and limited in clinical application. In this study, we used inverse-variance weighting to combine the hazard ratios for the four datasets and performed pathway analysis to identify prognosis-associated gene signatures. A total of 2,418 genes were found to be significantly associated with overall survival. Of these, a 21-gene signature in the HMGB1/RAGE signalling pathway and a 31-gene signature in the clathrin-coated vesicle cycle pathway were significantly associated with prognosis of lung adenocarcinoma across all four datasets (all p-values < 0.05, log-rank test). We combined the scores for the three pathways to derive a combined pathway-based risk (CPBR) score. Three pathway-based signatures and CPBR score also had more predictive power than single genes. Finally, the CPBR score was validated in two independent cohorts (GSE14814 and GSE13213 in the GEO database) and had significant adjusted hazard ratios 2.72 (p-value < 0.0001) and 1.71 (p-value < 0.0001), respectively. These results could provide a more complete picture of the lung cancer pathogenesis.

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Figures

Figure 1

Figure 1. Using HMGB1/RAGE signalling pathway-based signatures as prognosis predictor, Kaplan-Meier survival analysis of patients with lung adenocarcinoma were performed in all four training datasets (CAN/DF, HLM, UK, MSK) and in the two validation cohorts (GSE14814 and GSE1321).

Figure 2

Figure 2. Using pathway-based signatures of beta-adrenergic receptor regulation of the ERK pathway as prognosis predictor, Kaplan-Meier survival analysis of patients with lung adenocarcinoma were performed in all four training datasets (CAN/DF, HLM, UK, and MSK) and in the two validation cohorts (GSE14814 and GSE1321).

Figure 3

Figure 3. Using pathway-based signatures of clathrin-coated vesicle cycle pathway as prognosis predictor, Kaplan-Meier survival analysis of patients with lung adenocarcinoma were performed in all four training datasets (CAN/DF, HLM, UK, and MSK) and in the two validation cohorts (GSE14814 and GSE1321).

Figure 4

Figure 4. Using combined pathway-based risk (CPBR) score as prognosis predictor, based on the combined risk scores for the three individual pathways, results of survival analysis were shown that overall survival was significantly different between high-risk group and low-risk group in (a) the CAN/DF dataset, (b) the HLM dataset, (c) the UM dataset, (d) the MSK dataset and (e) the validation cohort of GSE14814 (f) the validation cohort of GSE1321, respectively.

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