Lung cancer is the most common malignancy worldwide. Thus, there is a critical need for diagnostic biomarkers with adequate sensitivity and specificity for lung cancer detection. Glycans in glycoproteins are significantly altered in cancer, and may serve as a tool for identifying potential diagnostic biomarkers. Recent studies have reported changes in α-1-antitrypsin (A1AT) glycosylation in lung cancer serum, tissue and cell lines. In this study, a lectin microarray was used to detect glycosylation changes in serum A1AT from patients with lung adenocarcinoma (ADC), squamous cell lung cancer, small-cell lung cancer (SCLC) and benign pulmonary diseases. Differentially expressed glycosylated patterns of A1AT were identified by lectin arrays and were confirmed by lectin-based enzyme-linked immunosorbent assay (ELISA). We found that galactosylated A1AT could distinguish non-small-cell lung cancer (NSCLC) from benign pulmonary diseases (AUC = 0.834); fucosylated A1AT showed exceptional capability in distinguishing ADC from benign diseases (AUC = 0.919) or other lung cancer subtypes (AUC = 0.844), and A1AT containing poly-LacNAc could detect SCLC from benign diseases (AUC = 0.905) or NSCLC (AUC = 0.707). The present study indicates that glycosylated patterns of A1AT may serve as potential biomarkers for detection of lung cancer. Further studies in larger sample sizes are necessary to validate the clinical utility of these markers.

Biomarkers in the Lung Cancer Diagnosis: A Clinical Perspective

Copper transporter family proteins may regulate the chemoresistance of non-small cell lung cancer (NSCLC) to platinum-based anticancer drugs. The present study aimed to investigate the expression of these proteins in lung cancer tissue specimens for association with clinicopathological data and patient responses to chemotherapy and survival. A total of 54 patients with surgically resected NSCLC that received first-line platinum-based doublet chemotherapy were recruited in the present study, and the paraffin-embedded pre-treatment tumor tissue specimens were subjected to immunohistochemical analysis for the expression of human copper transporter 1 (hCtr1) and copper-transporting p-type adenosine triphosphatase 1 (ATP7A) and 2 (ATP7B). This cohort of patients with NSCLC received platinum-based chemotherapy subsequent to the surgical removal of tumor lesions. ATP7B expression was found to be significantly associated with tumor cell differentiation, while hCtr1 expression was significantly associated with improved chemotherapeutic responses. The median survival time was 20 months in patients possessing tumors with high ATP7A expression, but >66 months in patients possessing tumors with low ATP7A expression at the end of the follow-up (P66 months in patients with high tumor hCtr1 expression (P<0.001). High hCtr1 and low ATP7A expression were each favorable prognostic factors subsequent to chemotherapy for patients with resected NSCLC. Multivariate analysis revealed that high hCtr1 expression combined with low ATP7A expression, good tumor differentiation and female gender were all favorable independent predictive and prognostic factors for patients with resected NSCLC following chemotherapy. High hCtr1 expression combined with low ATP7A expression was associated with an improved prognosis in patients with resected NSCLC that received platinum-based chemotherapy. Surgery combined with neoadjuvant chemotherapy may improve the survival time of patients with NSCLC.