Abstract:Abstract. The p16 protein is a cyclin-dependent kinase (CDK) inhibitor, which plays an important role in the regulation of the cell cycle by inactivating the cyclin-dependent kinase (CDK) that phosphorylates the retinoblastoma (Rb) protein.Overexpression of p16 protein has been found in many types of human malignancy. Autoantibody response to p16 in cancer has not been reported. This study determined the extent and frequency of autoantibodies to p16 in diverse malignancies. p16 recombinant protein was expresse… Show more
“…Overexpression of p16 protein has been reported in several types of cancer, although normal tissues exhibit low or undetectable levels (18,23). This is possibly a feedback reaction to the development of malignancy in the body.…”
Section: Discussionmentioning
confidence: 99%
“…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 they observed a significant increase in the prevalence of IgG antibodies to the p16 protein in breast cancer.…”
Section: Introductionmentioning
confidence: 99%
“…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 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).…”
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 ...
“…Overexpression of p16 protein has been reported in several types of cancer, although normal tissues exhibit low or undetectable levels (18,23). This is possibly a feedback reaction to the development of malignancy in the body.…”
Section: Discussionmentioning
confidence: 99%
“…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 they observed a significant increase in the prevalence of IgG antibodies to the p16 protein in breast cancer.…”
Section: Introductionmentioning
confidence: 99%
“…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 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).…”
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 ...
“…An increase to 44% sensitivity and 97.6% specificity in breast cancer detection was achieved through the successive addition of the three TAAs p53, protein 16 (p16), and avian myelocytomatosis viral oncogene homolog (c-myc; ref. 81). SEREX technology was used by Zhong and colleagues (82) to detect three further breast cancer-associated autoantibodies including serine active site containing 1 (SERAC1), receptor expressed in lymphoid tissues (RELT), and ankyrin repeat and suppressor of cytokine signaling (SOCS) box protein 9 (ASB-9).…”
Current diagnostic techniques used for the early detection of cancers are successful but subject to detection bias. A recent focus lies in the development of more accurate diagnostic tools. An increase in serologic autoantibody levels has been shown to precede the development of cancer disease symptoms. Therefore, autoantibody levels in patient blood serum have been proposed as diagnostic biomarkers for early-stage diagnosis of cancers. Their clinical application has, however, been hindered by low sensitivity, specificity, and low predictive value scores. These scores have been shown to improve when panels of multiple diagnostic autoantibody biomarkers are used. A five-marker biomarker panel has been shown to increase the sensitivity of prostate cancer diagnosis to 95% as compared with 12.2% for prostate-specific antigen alone. New potential biomarker panels were also discovered for lung, colon, and stomach cancer diagnosis with sensitivity of 76%, 65.4%, and 50.8%, respectively. Studies in breast and liver cancer, however, seem to favor single markers, namely a-2-HS-glycoprotein and des-g-carboxyprothrombin with sensitivities of 79% and 89% for the early detection of the cancers. The aim of this review is to discuss the relevance of autoantibodies in cancer diagnosis and to outline the current methodologies used in the detection of autoantibodies. The review concludes with a discussion of the autoantibodies currently used in the diagnosis of cancers of the prostate, breast, lung, colon, stomach, and liver. A discussion of the potential future use of autoantibodies as diagnostic cancer biomarkers is also included in this review. Cancer Epidemiol Biomarkers Prev; 22(12); 2161-81. Ó2013 AACR.
“…With the successive addition of TAAs to a final total of seven antigens, there was stepwise increase of positive antibody reactions up to 56.9 percent in HCC. In our recent study, p16, a cyclin-dependent kinase inhibitor, which has been implicated as an important tumor suppressor [33], was evaluated as a TAA and added into our previously constituted mini-array of seven TAAs [24]. As shown in Table 1, the frequency of antibodies to eight TAAs in sera from patients with chronic hepatitis, liver cirrhosis and HCC using Enzyme-linked immunosorbent assay (ELISA).…”
Section: Using a Mini-array Of Multiple Taas To Enhance Antibody Detementioning
Liver cancer, especially hepatocellular carcinoma (HCC), is particularly prevalent in Africa and Asia. HCC affects the Hispanic population of the United States at a rate double that of the white population. The majority of people with HCC will die within 1 year of its detection. This high case-fatality rate can in part be attributed to lack of diagnostic methods that allow early detection. How to establish a methodology to identify the high-risk individuals for HCC remains to be investigated. The multifactorial and multi-step nature in the molecular pathogenesis of human cancers must be taken into account in both the design and interpretation of studies to identify markers which will be useful for early detection of cancer. Our recent studies demonstrated that a mini-array of multiple tumorassociated antigens (TAAs) might enhance autoantibody detection for diagnosis of HCC, especially for the alpha fetoprotein (AFP)-negative cases. It also suggested that different types of cancer might require different panels of TAAs to achieve the sensitivity and specificity required to make immunodiagnosis a feasible adjunct to tumor diagnosis.
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