Humoral immune response to tumor-associated antigen Ubiquilin 1 (UBQLN1) and its tumor-promoting potential in lung cancer

Background: The aim of this study is to investigate the expression of UBQLN1 in lung cancer (LC) tissue and the diagnostic capability of autoantibody to UBQLN1 (anti-UBQLN1) in the detection of LC, as well as discriminating malignant and benign pulmonary nodules (PNs). Methods Sera from 798 participants of three independent cohorts were used to discover and validate the level of autoantibodies via HuProt microarray and Enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was applied to establish model combining anti-UBQLN1, CT characteristics and traditional serum biomarkers. Receiver operating characteristic curve (ROC) analysis was performed to evaluate the diagnostic potential. Immunohistochemistry of tissue array was performed to detect UBQLN1 expression in 88 LC tissues and 88 para-tumor tissues. qRT-PCR and western blotting were performed to detect the expression of UBQLN1 at the mRNA and protein levels in cell lines, respectively. Trans-well assay and cell counting kit-8 (CCK-8) was used to investigate the functions of UBQLN1 in two lung cancer cell lines (CALU3 and H358). Results Anti-UBQLN1 was identified with the highest fold change by means of protein microarray in the discovery cohort. The level of anti-UBQLN1 in LC patients was obviously higher than that in NC or patients with benign lung disease of validation cohort 1 (P < 0.05). The area under the curve (AUC) of anti-UBQLN1 was 0.610 (95%CI: 0.508–0.713) while reached at 0.822 (95%CI: 0.784–0.897) when combining anti-UBQLN1with CEA, CYFRA21-1, CA125 and three CT indicators (vascular notch sign, lobulation sign and mediastinal lymph node enlargement) in the discrimination of malignant from benign PNs. UBQLN1 protein was overexpressed in lung adenocarcinoma (LUAD) tissues compared to para-tumor tissues. UBQLN1 knockdown remarkably inhibited the migration, invasion and proliferation of two lung cancer cell lines. Conclusions UBQLN1 can elicit the humoral immune response as tumor-associated antigen in LC. The autoantibody to UBQLN1 might be a potential biomarker for LC diagnosis and might be useful to improve the discrimination of malignant from benign PNs.