Morphologic assessment of lung
tumors is informative but insufficient to adequately predict patient outcome. We previously identified transcriptional profiles that predict patient survival, and here we identify
proteins associated with patient survival in
lung adenocarcinoma. A total of 682 individual
protein spots were quantified in 90
lung adenocarcinomas by using quantitative two-dimensional
polyacrylamide gel electrophoresis analysis. A leave-one-out cross-validation procedure using the top 20 survival-associated
proteins identified by Cox modeling indicated that
protein profiles as a whole can predict survival in stage I
tumor patients (P = 0.01). Thirty-three of 46 survival-associated
proteins were identified by using mass spectrometry. Expression of 12 candidate
proteins was confirmed as
tumor-derived with immunohistochemical analysis and tissue microarrays.
Oligonucleotide microarray results from both the same
tumors and from an independent study showed mRNAs associated with survival for 11 of 27 encoded genes. Combined analysis of
protein and
mRNA data revealed 11 components of the glycolysis pathway as associated with poor survival. Among these candidates,
phosphoglycerate kinase 1 was associated with survival in the
protein study, in both
mRNA studies and in an independent validation set of 117
adenocarcinomas and squamous lung
tumors using tissue microarrays. Elevated levels of
phosphoglycerate kinase 1 in the serum were also significantly correlated with poor outcome in a validation set of 107 patients with
lung adenocarcinomas using ELISA analysis. These studies identify new prognostic
biomarkers and indicate that
protein expression profiles can predict the outcome of patients with early-stage
lung cancer.