Circulating antibodies to p16 protein-derived peptides in breast cancer

Abstract

Abstract. Overexpression of the p16 protein has been reported in breast cancer and may trigger the secretion of antibodies against itself. Circulating anti-p16 antibodies that were detected with a recombinant protein have been reported in breast cancer. The present study was designed to determine whether the levels of circulating IgG antibody to p16 protein-derived linear antigens are altered in breast cancer. An enzyme-linked immunosorbent assay (ELISA) was developed in-house to determine circulating IgG against peptide antigens derived from the p16 protein in 152 female breast cancer patients and 160 healthy female subjects. The Student's t-test revealed that breast cancer patients exhibited significantly higher levels of anti-p16 IgG antibody compared to control subjects (t=2.02, P=0.045). In addition, ductal cancer appeared to be the main type contributing to the increased levels of circulating anti-p16 antibodies (t=2.08, P=0.038). Of all four stages of breast cancer, stage I was associated with the highest levels of IgG antibody (t=2.02, P=0.045) and receiver operating characteristic (ROC) analysis demonstrated that the area under the ROC curve was 0.74 (95% confidence interval: 0.65-083) and that the sensitivity against a specificity of 90% was 30.3%. Therefore, the levels of circulating IgG antibody to the p16 protein may be a potential biomarker for early diagnosis of breast cancer. IntroductionThere is convincing evidence suggesting that circulating autoantibodies for cancer have diagnostic potential (1-6). A successful test has been developed for early diagnosis of lung cancer (7-9). Breast cancer is a common malignant condition, mainly occurring in women, and the leading cause of cancer-related mortality among women, accounting for 23% of all female cancer cases worldwide (10). Although breast cancer is easy to diagnose by microscopic analysis of a sample, i.e., biopsy, early diagnosis of this malignancy is crucial. Circulating autoantibodies have been suggested to serve as biomarkers for the early diagnosis of breast cancer (11,12), but their sensitivity and specificity have not been satisfactory. Thus, it is crucial to identify a panel of useful tumor-associated antigens (TAAs) in order to develop antibody-based tests for the early diagnosis of breast cancer.The p16 protein is a cyclin-dependent kinase (CDK) inhibitor that has been found to be involved in the downregulation of the cell cycle through the inactivation of CDK (13-15). As this CDK inhibitor mainly plays a role in suppressing CDK4 and CDK6 activity and arresting cells during the G1 phase of the cell cycle (14,16), it is associated with the unrestrained growth that is the hallmark of cancer (17). A number of studies have suggested that the levels of circulating antibodies to the p16 protein are increased in patients with breast cancer (11,18,19). For example, Looi et al developed an in-house enzyme-linked immunoassay (ELISA) using recombinant p16 protein as antigens to detect anti-p16 IgG levels in the plasma of cancer patients (18) and ...

Further study of circulating IgG antibodies to CD25‐derived peptide antigens in nonsmall cell lung cancer

“…Circulating anti-CD25 IgG was detected with a modified ELISA method that was developed using a linear peptide antigen derived from human CD25 protein according to previous studies [13][14][15][16][17]; a control antigen was designed based on a maize protein (NCBI accession 1BFA_A), and its sequence is as follows:…”

Inhibitory Effects of Circulating Natural Autoantibodies to CD47-derived Peptides on Oral Squamous Cell Carcinoma Cells

“…Natural autoantibodies are considered to be important antitumor systems in vivo,showing a decrease in earlystage cancer patients while a gradual increase during the tumor progresses [18,25]. A number of studies have been concerned about the role of natural autoantibodies in NSCLC, esophageal cancer, breast cancer and liver cancer, including those for p16, FOXP3, CD25, ABCC3, ANXA1, BIRC5, MYC and VEGFR1 [18,[25][26][27][28][29]. It has been supposed that natural autoantibodies may be useful anticancer agents for postoperative therapies to prevent the recurrence of human cancer.…”

Inhibitory Effects of Circulating Natural Autoantibodies to CD47-derived Peptides on Oral Squamous Cell Carcinoma Cells

“…Natural autoantibodies are considered to be important antitumor systems in vivo showing a decrease in early-stage cancer patients while a gradual increase during the tumor progresses [18,25]. A number of studies have been concerned about the role of natural autoantibodies in NSCLC, esophageal cancer, breast cancer and liver cancer, including those for p16, FOXP3, CD25, ABCC3, ANXA1, BIRC5, MYC and VEGFR1 [18,[25][26][27][28][29]. It has been supposed that natural autoantibodies may be useful anticancer agents for postoperative therapies to prevent the recurrence of human cancer.…”