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.
Highlights
Lung cancer is the most frequent malignancy, with the highest incidence and mortality in both sexes worldwide, accounting for approximately 2.1 million new cases (11.6% of all tumors) diagnosed and 1.8 million deaths (18.4% of all tumors) per year globally, which seriously endangers human health [1]
Alterations in Bronchoalveolar lavage fluid (BALF) Glycopatterns Among benign pulmonary diseases (BPD), ADC, squamous carcinomas (SCC), and small cell lung cancer (SCLC) Detected by Lectin Microarrays
To identify the abnormal glycopatterns associated with lung cancer, all samples from BPD, ADC, SCC, and SCLC were separately detected using lectin microarrays
Summary
Lung cancer is the most frequent malignancy, with the highest incidence and mortality in both sexes worldwide, accounting for approximately 2.1 million new cases (11.6% of all tumors) diagnosed and 1.8 million deaths (18.4% of all tumors) per year globally, which seriously endangers human health [1]. Bronchoalveolar lavage fluid (BALF), a type of proximal biofluid routinely obtained from the segmental bronchus of interest during flexible fiberoptic bronchoscopy in individuals with suspected pulmonary disease, has been considered as a useful, safe and minimally invasive biological specimen for lung cancer biomarker discovery [17]. By utilizing this approach, airway components can be recovered from a large area of lung parenchyma [18]. Detection of proteins in BALF from patients with lung cancer can provide direct information on exposure within the lung
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