Protein Glycopatterns in Bronchoalveolar Lavage Fluid as Novel Potential Biomarkers for Diagnosis of Lung Cancer

Lina Liu; Dan Li; Jian Shu; Li Wang; Fan Zhang; Chen Zhang; Hanjie Yu; Mingwei Chen; Zheng Li; Xuan Guo

doi:10.3389/fonc.2020.568433

Protein Glycopatterns in Bronchoalveolar Lavage Fluid as Novel Potential Biomarkers for Diagnosis of Lung Cancer

Front Oncol. 2021 Jan 14:10:568433. doi: 10.3389/fonc.2020.568433. eCollection 2020.

Authors

Lina Liu^{1

2}, Dan Li³, Jian Shu⁴, Li Wang³, Fan Zhang⁴, Chen Zhang⁴, Hanjie Yu⁴, Mingwei Chen³, Zheng Li⁴, Xuan Guo²

Affiliations

¹ Department of Clinical Laboratory, Xi'an No. 4 Hospital, Xi'an, China.
² Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
³ Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁴ Laboratory for Functional Glycomics, College of Life Sciences, Northwest University, Xi'an, China.

Abstract

Lung cancer is one of the most prevalent and life-threatening neoplasias worldwide due to the deficiency of ideal diagnostic biomarkers. Although aberrant glycosylation has been observed in human serum and tissue, little is known about the alterations in bronchoalveolar lavage fluid (BALF) that are extremely associated with lung cancer. In this study, our aim was to systematically investigate and assess the alterations of protein glycopatterns in BALF and possibility as biomarkers for diagnosis of lung cancer. Here, lectin microarrays and blotting analysis were utilized to detect the differential expression of BALF glycoproteins from patients with 80 adenocarcinomas (ADC), 77 squamous carcinomas (SCC), 51 small cell lung cancer (SCLC), and 73 benign pulmonary diseases (BPD). These 281 specimens were then randomly divided into a training cohort and validation cohort for constructing and verifying the diagnostic models based on the glycopattern abundances. Moreover, an independent test was performed with 120 newly collected BALF samples enrolled in the double-blind cohort to further assess the clinical application potential of the diagnostic models. According to the results, there were 15 (e.g., PHA-E, EEL, and BPL) and 14 lectins (e.g., PTL-II, LCA, and SJA) that individually showed significant variations in different types and stages of lung cancer compared to BPD. Notably, the diagnostic models achieved better discriminate power in the validation cohort and exhibited high accuracies of 0.917, 0.864, 0.712, 0.671, and 0.781 in the double-blind cohort for the diagnosis of lung cancer, early stage lung cancer, ADC, SCC, and SCLC, respectively. Taken together, the present study revealed that the abnormally altered protein glycopatterns in BALF are expected to be novel potential biomarkers for the identification and early diagnosis of lung cancer, which will contribute to explain the mechanism of the development of lung cancer from the perspective of glycobiology.

Keywords: bronchoalveolar lavage fluid; diagnostic model; lectin microarray; lung cancer; protein glycosylation.