Abstract
Lung adenocarcinoma is the most often diagnosed cancer and the primary cause of cancer death worldwide. Chemotherapy for lung cancer is still main treatment. However, a response rate is very low. In this study, we aim to identify serum protein indicator for predicting response to a platinum plus anti-metabolite regimen through integrative analysis of transcriptomics and proteomics. Methods: A total of 27 patients with lung ADC (17 non-responders, NR and 10 responders, R) receiving a combination of carboplatin and gemcitabine treatment was included. For transcriptomic study, RNA was extracted from the frozen biopsy tissue of patients. Sequencing was performed on the Illumina/HiSeq2000 platform and differentially expressed genes were converted to proteins using UniProt database. For proteomic study, serum from 6 responders and 6 non-responders was subjected to the label-free liquid chromatography tandem mass spectrometry. Blood-based proteins reflecting the tissue-specific biomarker were obtained using Venn diagrams. Candidate proteins were validated by western blotting. Results: We found that 417 genes, including 52 up-regulated genes and 365 down-regulated genes were differentially expressed. In addition, we also showed that there were 26 up-regulated proteins and 5 down-regulated proteins. Based on integrative analysis, alpha-1-acid glycoprotein (A1AG1) and fibrinogen alpha chain (FIBA) were detected in both tissue and serum of patients, with a higher level in responders than non-responders. Additionally, serum expression level of A1AG1 and FIBA was shown to be link chemotherapeutic response. Conclusion: A1AG1 and FIBA indicating as tissue-specific biomarkers may be used for identifying ADC patients who would benefit from the platinum plus antimetabolite treatment.
