Table 1.
Proteomic analysis based on BALF for lung cancer
| Study subjects | Proteomic analysis | Validation subjects | Validation method | Specific proteins (numbers/name) | Comments | Ref. |
|---|---|---|---|---|---|---|
| NSCLC (n = 6) and control (n = 16) | MALDI-TOF/TOF MS | NA | NA | 2/HTN3 and S100A12 | HTN3 and S100A12 were significantly upregulated in the BALF of NSCLC patients. | 58 |
| COPD (n = 15), NSCLC (n = 15), NSCLC with COPD (n = 15), and control group with neither NSCLC nor COPD (n = 15) | 2D-PAGE and MALDI-TOF/TOF MS | Paired BALF proteins | Western blot | 1/AKR1B10 | Compared with the control group, the expression of AKR1B10 was increased in the NSCLC group, while no difference was detected in the COPD group. | 59 |
| Lung adenocarcinoma (n = 4) and benign lung diseases (n = 4) | iTRAQ labeling and LC-MS/MS | Lung adenocarcinoma (n = 18), lung SQCC (n = 9), SCLC (n = 6), and benign lung diseases (n = 6) | ELISA in BALF samples | 1/Napsin A | The protein level of Napsin A was significantly increased in BALF of adenocarcinoma. | 60 |
| Lung cancer (n = 139) and benign lung diseases (n = 49) | 2D-PAGE and MS | Lung cancer (n = 204) and benign lung diseases (n = 48) | Bead-based immunoassays in BALF samples. | 5/APOA1, CO4A, CRP, GSTP1, SAMP | The levels of these five proteins led to a lung cancer diagnostic panel with 95% Sn and 81% Sp. | 61 |
| 2/STMN1 and GSTP1 | The quantification of these two proteins differentiated NSCLC and SCLC patients with 90% Sn and 57% Sp. | |||||
| Lung adenocarcinoma (n = 8) and non-tumor patients (n = 8) | LC-MS/MS | NA | NA | 33/S100-A8, TYMP, annexin A1, annexin A2, and TG2 | These five proteins of the DEPs were associated with lung cancer progression in previous studies and may be potential biomarkers for lung adenocarcinoma. | 62 |
| Lung adenocarcinoma (n = 12) and non-tumor patients (n = 10) | SWATH DIA MS† | NA | NA | 44/HPT, CO4A, GTSP1 | Three of the DEPs that we suggest as potential biomarkers were consistent with previous studies using BALF samples. | 63 |
| NSCLC (n = 26) and non-tumor patients (n = 16) | Label-free MS | NSCLC (n = 46) and non-tumor patients (n = 26) | ELISA in plasma | 3/Cystatin-C, Lipocalin-2, TIMP-1 | These three proteins were upregulated in BALF of NSCLC patients, and the results were confirmed in plasma. | 64 |
| Lung adenocarcinoma (n = 5), lung SQCC (n = 4), SCLC (n = 4), and benign lung diseases (n = 3) | MS-based quantitative N-glycoproteomic | Lung adenocarcinoma (n = 18), lung SQCC (n = 9), SCLC (n = 6), and benign lung diseases (n = 6) | ELISA in BALF | 1/Periostin | The expression of periostin was increased in BALF from all three tumor types, which is in agreement with the observation of elevated serum levels of this protein in a previous study. | 65 |
| SCLC (n=5): tumor-bearing lungs and non-tumor lungs | TMT-based quantitative MS | Paired tumor tissues | IHC in SCLC tissues | 4/DSTN, RNPEP, CNDP2, and CA1 | These four proteins were upregulated in BALF from tumor-bearing lungs and tumor tissues. | 66 |
| NA | SCLC-CellMiner resource‡ | 2/CNDP2 and RNPEP | 1. CNDP2 and RNPEP appeared to be potential indicators for ASCL1-high and NEUROD1-high subtypes of SCLC. 2. CNDP2 was found to be positively correlated with responses to etoposide, carboplatin, and irinotecan. |
NSCLC, non-small-cell lung cancer; MALDI-TOF/TOF, matrix-assisted laser desorption/ionization time of flight; MS, mass spectrometry; NA, not available; COPD, chronic obstructive pulmonary disease; 2D-PAGE, two-dimensional polyacrylamide gel electrophoresis; iTRAQ, isobaric tags for relative and absolute quantitation; LC-MS/MS, liquid chromatography tandem mass spectrometry; SQCC, squamous cell carcinoma; SCLC, small cell lung cancer; SWATH, sequential windowed acquisition of all theoretical fragment ion mass spectra; DIA, data-independent acquisition; ELISA, enzyme-linked immunosorbent assay; Sn, sensitivity; Sp, specificity; DEPs, differentially expressed proteins; TMT, tandem mass tags; IHC, immunohistochemistry.
†Indicates the analysis of BALF proteins by LC–MS/MS combining a simple sample pre-treatment and a DIA approach.
‡Indicates a bioinformatic resource for SCLC cell line genomics and pharmacology based on genomic signatures (https://discover.nci.nih.gov/rsconnect/SclcCellMinerCDB/).