Proteomic Analysis of the Air-Way Fluid in Lung Cancer. Detection of Periostin in Bronchoalveolar Lavage (BAL)

Abstract

Background: Bronchoalveolar lavage (BAL) is a specific type of airway fluid. It is a commonly used clinical specimen for the diagnosis of benign diseases and cancers of the lung. Although previous studies have identified several disease-associated proteins in the BAL, the potential utility of BAL in lung cancer is still not well-studied. Based upon the fact that the majority of secreted proteins are glycoproteins, we have profiled N-glycoproteins in BAL collected from lung cancers, and investigated the expression of glycoproteins such as the matrix N-glycoprotein, periostin, in lung cancers. Methods: BAL specimens (n = 16) were collected from lung cancer patients, and analyzed using mass spectrometry-based quantitative N-glycoproteomic technique. Additional BAL specimens (n = 39) were independently collected to further evaluate the expression of periostin by using an enzyme-linked immunosorbent assay (ELISA). Results: A total of 462 glycoproteins were identified in BAL samples using N-glycoproteomic technique, including 290 in lung adenocarcinoma (ADC, n = 5), 376 in squamous cell carcinoma (SQCC, n = 4), 309 in small cell lung carcinoma (SCLC, n = 4), and 316 in benign lung disease (n = 3). The expressions of several glycoproteins were elevated, including 8 in ADC, 12 in SQCC, and 17 in SCLC, compared to benign BALs. The expression of periostin was detected in all subtypes of lung cancers. To further investigate the expression of periostin, an ELISA assay was performed using additional independently collected BALs (n = 39) The normalized levels of periostin in benign disease, ADC, SQCC, and SCLC were 255 ± 104 (mean ± SE) and 4,002 ± 2,181, 3,496 ± 1,765, and 1,772 ± 1,119 ng/mg of total BAL proteins. Conclusion: Our findings demonstrate that proteomic analysis of BAL can be used for the study of cancer-associated extracellular proteins in airway fluid from lung cancer patients.

Bronchoalveolar lavage fluid assessment facilitates precision medicine for lung cancer

“…The MS-based quantitative N-glycoproteomic technique was also used to analyze BALF samples, revealing periostin in all samples from lung cancer patients. Validation of the screened periostin with ELISA in another 39 BALF samples also yielded the same conclusion 65 .…”

Diagnostic value of periostin in lung cancer‐related malignant pleural effusion

“…Recent studies have shown that elevated levels of POSTN were detected in the serum of patients with different types of malignancies, indicating that it would be an effective diagnostic and prognostic biomarker 34 . It was also demonstrated that POSTN could be detected in bronchoalveolar lavage of patients with lung cancer, and the POSTN level in the bronchoalveolar lavage was significantly higher than that in benign lung disease 35 . In this study, our results demonstrated that the level of serum POSTN was upregulated in patients with lung cancer‐related MPE compared to patients with BPE, which is consistent with previous studies by Xu et al21 and Zhang et al 22 Their studies indicated that serum POSTN levels were significantly increased in patients with NSCLC when compared to patients with benign lung diseases and healthy controls, and high levels of serum POSTN were associated with poor prognosis of patients with NSCLC.…”

Periostin: A Potential Biomarker and Therapeutic Target in Pulmonary Diseases

“…A clinical trial conducted by Nakamura et al (UMIN000012339) demonstrated that periostin and squamous cell carcinoma antigen were highly expressed during the pathogenesis of acute bronchitis caused by respiratory syncytial virus (RSV), and they were associated with the subsequent development of asthma. In a recent study, proteomic analysis, and ELISA assay of periostin in BAL fluid of lung cancer patients showed increasing periostin levels in all subtypes of lung cancer (67).…”

“…Lung cancer patients BALF Proteomic analysis and ELISA assay of BALF showed increasing in periostin expression in all subtypes of lung cancers (67). with eosinophilic asthma and persistent airflow limitation (37).…”