Autoantibodies against p16 protein-derived peptides may be a potential biomarker for non-small cell lung cancer

Zhang, Cong; Ye, Leiguang; Guan, Shaopeng; Jin, Shunzi; Wang, Weili; Sun, Shilong; Lee, Kuang-Hui; Wei, Jun; Liu, Baogang

doi:10.1007/s13277-013-1271-4

Cited by 20 publications

(21 citation statements)

References 16 publications

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“…Other TAAbs were excluded from the review because relevant data were available from fewer than 3 articles . Five of the included studies examined only small-cell lung cancer (SCLC) [45,50,52,58,67], and eight included only non-small cell lung cancer (NSCLC) [28,47,54,55,57,59,64,109]. A total of 50 articles were based on serum specimens, while the remaining 3 were based on plasma samples.…”

Section: Basic Information About the Included Studiesmentioning

confidence: 99%

Diagnostic Value of Autoantibodies in Lung Cancer: a Systematic Review and Meta-Analysis

Qin¹,

Zeng²,

Yang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Recently, many studies have demonstrated that various tumor-associated autoantibodies have been detected in early stages of lung cancer. Therefore, we conducted a meta-analysis to comprehensively evaluate available evidence on the diagnostic value of autoantibodies against tumor-associated antigens in lung cancer. Methods: We systematically searched PubMed, Scopus, Web of Science and other databases through 23 March 2018. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. We used the bivariate mixed-effect models to calculate pooled values of sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, diagnostic odds ratios and associated 95% confidence intervals. Summary receiver operating characteristic (SROC) curves were used to summarize overall test performance. Deek’s funnel plot was used to detect publication bias. Results: Review of 468 candidate articles identified fifty-three articles with a total of 11,515 patients for qualitative review and meta-analysis. Pooled sensitivity, specificity and area under the SROC curve were as follows for tumor-associated autoantibodies against the following proteins: p53, 0.19, 0.98, 0.82; NY-ESO-1, 0.17, 0.98, 0.90; Survivin, 0.19, 0.99, 0.96; c-myc, 0.14, 0.98, 0.45; Cyclin B1, 0.18, 0.98, 0.91; GBU4-5, 0.07, 0.98, 0.91; CAGE, 0.14, 0.98, 0.90; p16, 0.08, 0.97, 0.91; SOX2, 0.14, 0.99, 0.93; and HuD, 0.17, 0.99, 0.82. Conclusion: Each tumor-associated autoantibody on its own showed excellent diagnostic specificity for lung cancer but inadequate sensitivity. Our results suggest that combinations or panels of tumor-associated autoantibodies may provide better sensitivity for diagnosing lung cancer, and the diagnostic accuracy of tumor-associated autoantibodies should be validated in more studies.

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Section: Basic Information About the Included Studiesmentioning

confidence: 99%

Diagnostic Value of Autoantibodies in Lung Cancer: a Systematic Review and Meta-Analysis

Qin¹,

Zeng²,

Yang³

et al. 2018

Cell Physiol Biochem

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“…The autoantibody specific for FOXP3 protein was measured by a relative ELISA approach as described in our recent publication [11][12][13][14][15][16]. To reduce the interference from a non-specific signal produced by passive absorption of various IgG antibodies in plasma to the surface of a 96-well microplate, a specific binding index (SBI) was used to express the levels of circulating autoantibody against FOXP3.…”

Section: Autoantibody Testingmentioning

confidence: 99%

“…For example, the level of ABCC3 autoantibodies in patients with lung and esophageal cancers [11,12], p16 autoantibodies in patients with esophageal cancer and non-small-cell lung cancer [13,14], ANXA1 autoantibodies in patients with lung cancer [15] and FOXP3 autoantibodies in patients with esophageal cancer [16] are significantly higher than in healthy subjects. However, only a few studies on autoantibodies in patients with cervical cancer have been reported.…”

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confidence: 99%

FOXP3 autoantibody as a potential early prognostic serum biomarker in patients with cervical cancer

Huangfu

Jia

et al. 2015

Int J Clin Oncol

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“…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 they observed a significant increase in the prevalence of IgG antibodies to the p16 protein in breast cancer. Based on our recent studies, the application of linear peptides as antigens may be more sensitive for ELISA in studying circulating antibodies against certain TAAs (20)(21)(22). Linear peptide antigens may be completely exposed and specifically bound to the corresponding antibodies.…”

Section: Introductionmentioning

confidence: 99%

“…ELISA was developed in-house using a linear peptide antigen, as described in our recent publications, in order to detect circulating IgG to linear peptide antigens derived from the p16 protein (21,22). Briefly, the linear peptide antigen was synthesized by solid-phase chemistry, with a purity of >95%; a synthetic peptide (H-VFQKLKDLKDYGGVSLPEWVCIAFHTSG-OH) derived from a goat α-lactalbumin protein (accession 1FKV_A) was used as the control antigen.…”

Section: Introductionmentioning

confidence: 99%

Circulating antibodies to p16 protein-derived peptides in breast cancer

Chen

Huang

Zhang

et al. 2015

Molecular and Clinical Oncology

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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 ...

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Autoantibodies against p16 protein-derived peptides may be a potential biomarker for non-small cell lung cancer

Cited by 20 publications

References 16 publications

Diagnostic Value of Autoantibodies in Lung Cancer: a Systematic Review and Meta-Analysis

Diagnostic Value of Autoantibodies in Lung Cancer: a Systematic Review and Meta-Analysis

FOXP3 autoantibody as a potential early prognostic serum biomarker in patients with cervical cancer

Circulating antibodies to p16 protein-derived peptides in breast cancer

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