Detection of circulating natural antibodies against CD25, MUC1, and VEGFR1 for early diagnosis of non‐small cell lung cancer

Abstract

We previously demonstrated that a deficiency of natural antibodies against CD25, Mucin 1 (MUC1), and vascular endothelial growth factor receptor 1 (VEGFR1) could contribute to high risk of non-small cell lung cancer (NSCLC). This study was designed to investigate whether natural IgG antibodies against POU domain class 5 transcription factor 1 (POU5F1), tumor necrosis factor-a (TNF-a), and the combination of CD25, VEGFR1, and MUC1 could play an anti-tumorigenic role against developing NSCLC. An ELISA was developed in-house to examine plasma IgG against peptide antigens derived from POU5F1, TNF-a, and a combination of peptide antigens derived from CD25, MUC1, and VEGFR1 in 211 patients with NSCLC and 200 healthy controls. Mann-Whitney U test demonstrated that plasma IgG levels for the combination of peptide antigens derived from CD25, MUC1, and VEGFR1 were significantly lower in NSCLC patients than control subjects (Z = À12.978, P < 0.001) although plasma levels of IgG antibodies for POU5F1 and TNFa were not significantly changed. The in-house ELISA made with the CD25-MUC1-VEGFR1 combination had a sensitivity of 49.6% against a specificity of 95% to detect early-stage NSCLC. In conclusion, natural antibodies against the combination of CD25, VEGFR1, and MUC1 may be an effective biomarker for early diagnosis of NSCLC.According to the 2018 global cancer statistics report, lung cancer is the tumor with the highest incidence and mortality among men, while the third highest morbidity and the second leading cause of cancer death in women worldwide [1]. In 2011, the mortality rate of lung cancer patients in China was as high as 25% [2]. According to histopathological classification, lung cancer has been divided into small cell lung cancer (SCLC) and nonsmall cell lung cancer (NSCLC), in which NSCLC accounts for 85% with three subtypes, including adenocarcinoma, squamous cell carcinoma, and largecell carcinoma [3]. Although the diagnostic technology and treatment regimens of lung cancer have continuously been improving, the 5-year survival rate of all combined tumor stages is still less than 20% [4]. Therapeutic efficacy and prognosis of lung cancer are related to pathological stage. Patients with early-stage lung cancer can have a 5-year survival rate of 50% [5].

Anti-Cancer Auto-Antibodies: Roles, Applications and Open Issues

“…Interestingly, a deficiency of natural antibodies against CD25, Mucin 1 (MUC1), and vascular endothelial growth factor receptor 1 (VEGFR1) has been proposed to contribute to high risk of NSCLC. In fact, levels of auto-antibodies against these antigens have been found to be systematically lower in NSCLC patients than control subjects [ 86 ]. Impressively, an optimized panel with four biomarkers (CEA, CA125, Annexin A1-Ab, and Alpha enolase-Ab) was established presenting an area under the receiver operator characteristic curve of 0.897, a sensitivity of 86.5%, a specificity of 82.3%, a positive predictive value (PPV) of 88.3%, a negative predictive value (NPV) of 79.7%, and a diagnostic accuracy of 84.8% for the training group [ 87 ].…”

Inhibitory effects of circulating natural autoantibodies to CD47‐derived peptides on OSCC cells

“…Natural autoantibodies are an important component contributing to the anti‐tumor system in the body and have shown a decrease in circulating levels among patients with early stage cancer (Liu et al, 2020; Zhao et al, 2018). It has been supposed that natural autoantibodies may be useful anti‐cancer agents for postoperative therapies to prevent the recurrence of human cancer.…”

Expression of MUC1 in different tumours and its clinical significance (Review)

“…Another study suggested that the abnormal expression of MUC1 was correlated with the poor prognosis of patients with lung adenocarcinoma ( 23 ). Results indicate the potential utility of MUC1 as a clinical diagnostic marker and therapeutic target for lung adenocarcinoma through the contributing role in pathological features, such as development and invasive metastasis ( 24 ).…”