Hsinchu, Taiwan
Hsinchu, Taiwan

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Jin Y.,Jilin University | Guan S.,Jilin University | Liu L.,Jilin University | Sun S.,Jilin University | And 2 more authors.
Asia-Pacific Journal of Clinical Oncology | Year: 2015

Aim: Our recent work suggested that circulating IgG antibodies to a linear peptide derived from p16 protein were significantly increased in patients with lung cancer. The present study was then designed to test whether such autoantibodies were also altered in esophageal cancer. Methods: An enzyme-linked immunosorbent assay was developed in-house to determine circulating IgA and IgG antibodies against p16 protein-derived antigens in 97 patients with esophageal squamous cell carcinoma (ESCC) and 226 healthy subjects. Results: The levels of anti-p16 IgG but not IgA antibodies were significantly higher in the patient group than the control group (t=2.81, P=0.0052); circulating anti-p16 IgG levels were inversely correlated with stages of ESCC (r=-0.30, df=81, P=0.0058) and patients with stage I of ESCC had the highest IgG level among all four stages (t=5.25, P≤0.0001, compared with control subjects). There was no correlation between the levels of IgA and IgG either in the patient group (r=-0.05, df=86, P=0.627) or in the control group (r=-0.1, df=205, P=0.146). Conclusion: Circulating IgG autoantibody to p16 protein may be a potential biomarker for early diagnosis of esophageal cancer. © 2015 Wiley Publishing Asia Pty Ltd.


Xu S.,Jilin University | Huangfu M.,Jilin University | Jia X.,Jilin University | Song X.,Jilin University | And 4 more authors.
International Journal of Clinical Oncology | Year: 2015

Background: Overexpression of tumor-associated antigens has been reported in many types of cancer and may trigger secretion of their autoantibodies. The present work was designed to test whether circulating antibody to FOXP3 protein-derived antigens was altered in early cervical cancer and cervical benign tumors. Methods: A total of 141 patients with cervical cancer, 133 patients with cervical benign tumors and 148 healthy age-matched volunteers were recruited. The level of circulating anti-FOXP3 IgG antibody was tested using an enzyme-linked immunosorbent assay developed in-house with linear peptide antigens derived from FOXP3 protein. The linear peptide antigens were designed according to the computational prediction of HLA-II epitopes. Results: Student’s t test showed that anti-FOXP3 IgG in the malignant tumor group and the benign tumor group was significantly higher than in the control group (t = 6.127, p < 0.001; t = 2.704, p = 0.007). In addition, patients with stage I cervical cancer (t = 2.968, p = 0.003) had a significantly higher level of FOXP3 autoantibodies than patients with benign tumors. The sensitivity against >90 % specificity was 20.6 % with an interassay deviation of 11.7 % in the cervical cancer group. Based on a cut-off value determined by the 98th percentile of the control group IgG levels, the anti-FOXP3 IgG positivity was 2.1 % in patients with cervical cancer compared to 2.0 % in the health controls (chi-squared = 0.004, p = 0.952, OR = 1.051, 95 % CI 0.209–5.295). Conclusion: The circulating autoantibody to FOXP3 reflecting the continuous development of the cervical lesion, may be a potential biomarker with early prognostic values for cervical cancer. © 2015, Japan Society of Clinical Oncology.


Wang W.,Jilin University | Guan S.,Jilin University | Sun S.,Jilin University | Jin Y.,Jilin University | And 4 more authors.
Tumor Biology | Year: 2014

The EarlyCDT®-Lung test was the first autoantibody-based diagnostic tool for lung cancer, which was developed with a panel of recombinant protein antigens. To confirm whether the antibody test developed with linear peptide antigens has a similar power to that developed with the whole protein molecules, the present work was then undertaken to develop an in-house enzyme-linked immunosorbent assay with linear peptide antigens derived from annexin A1 (ANXA1) and DEAD box protein 53 (DDX53), which have been used to develop the EarlyCDT®-Lung test. A total of 272 patients with non-small cell lung cancer (NSCLC) and 227 control subjects matched in age and smoking history were recruited. Student's t test showed that the levels of circulating IgG to ANXA1-derived peptide antigens were significantly higher in patients with NSCLC than control subjects (t=5.66, P<0.0001), in which the increased anti-ANXA1 IgG levels were observed only in patients at stages I, II, or III, but not in those at stage IV. However, the levels of circulating IgG to DDX53-derived peptide antigens were not significantly altered in NSCLC (t=1.78, P=0.076). Receiver operating characteristic analysis showed that the sensitivity against specificity of >90% was 23.7% for ANXA1 IgG assay and 13.8% for DDX53 IgG assay. This work suggests that the linear peptide antigen derived from ANXA1 may be suitable for the development of diagnostic tool for lung cancer although further screening is needed to identify more such peptide antigens derived from tumor-associated antigens. © International Society of Oncology and BioMarkers (ISOBM) 2014.


Ye L.,Harbin Medical University | Guan S.,Jilin University | Zhang C.,Jilin University | Lee K.-H.,Pei Ling Guan Si Hospital | And 3 more authors.
Tumor Biology | Year: 2013

The present study was undertaken to develop a relatively quantitative enzyme-linked immunosorbent assay (ELISA) in-house using human leukocyte antigen class II-restricted epitopes in order to test circulating autoantibodies to human forkhead/winged helix transcription factor (FOXP3) as a biomarker for esophageal cancer. A total of 97 patients with esophageal squamous cell carcinoma (ESCC) and 227 healthy subjects were recruited for this study, and their plasma samples were collected for antibody analysis with the ELISA approach. Student's t test showed that the anti-FOXP3 IgG antibody levels were significantly higher in the patient group than the control group (t = 6.23, P < 0.0001). Based on a cutoff value determined by the mean + 3SD of control IgG levels, the positive rate was 5.15 % in patients with ESCC as compared to 0.88 % in control subjects (X 2 = 6.53, P = 0.019, OR = 5.85, 95 % CI 1.12-30.67), in which patients at stage I had the highest positivity (11.54 %, X 2 = 12.15, P = 0.0005, OR = 13.10, 95 % CI 2.09-82.04). The sensitivity against >95 % specificity was 22.7 % for the IgG assay with an inter-assay deviation of 13.35 %. This work suggests that circulating IgG autoantibody to FOXP3 may be a potential biomarker for early diagnosis of esophageal cancer. © 2013 International Society of Oncology and BioMarkers (ISOBM).


Ye L.,Harbin Medical University | Li X.,Harbin Medical University | Sun S.,Jilin University | Guan S.,Jilin University | And 5 more authors.
Clinical and Translational Oncology | Year: 2013

Purpose: Tumors can trigger specific immune response to tumor-associated antigens but the precise mechanism remains unclear. Since regulatory T-lymphocytes (Treg) play a crucial role in controlling autoimmune responses, the present work was undertaken to test whether dysfunction of Treg cells could be involved in developing autoimmunity in patients with lung cancer. Methods: In this study, we developed an in-house enzyme-linked immunosorbent assay to test circulating anti-CD25 autoantibodies among 272 patients with non-small cell lung cancer (NSCLC) and 226 control subjects matched in age, gender and smoking history. Results: Mann-Whitney U test showed that the anti-CD25 IgG level was significantly higher in patients with NSCLC than control subjects (Z = -7.48, P < 0.001) while the anti-CD25 IgA level was not significantly changed in the patient group as compared with the control group (Z = -1.34, P = 0.181). Spearman correlation analysis failed to reveal a significant correlation between the levels of anti-CD25 IgG and IgA either in patients with NSCLC (r = -0.034, P = 0.578) or in control subjects (r = 0.055, P = 0.429). ROC analysis showed an AUC of 0.70 for anti-CD25 IgG, in which NSCLC at stage III had the highest AUC (0.75). The sensitivity against a specificity of >90 % was 35.0 % for anti-CD25 IgG assay with an inter-assay deviation of 9.4 %, and 4.0 % for anti-CD25 IgA assay with an inter-assay deviation of 13.0 %. Conclusions: Circulating anti-CD25 IgG antibody may be a useful biomarker for prognosis of lung cancer. © 2012 Federación de Sociedades Españolas de Oncología (FESEO).


Guan S.,Jilin University | Liu B.,Harbin University | Zhang C.,Jilin University | Lee K.-H.,Pei Ling Guan Si Hospital | And 2 more authors.
Clinical and Translational Oncology | Year: 2013

Background: The present study was undertaken to develop an in-house enzyme-linked immunosorbent assay (ELISA) using human leukocyte antigen class II restricted epitopes to test circulating autoantibodies to CD25 as a biomarker for esophageal cancer. Methods: A total of 97 patients with esophageal squamous cell carcinoma (ESCC) and 226 healthy subjects were recruited for this study and their plasma samples were collected for antibody analysis with the ELISA approach. Results: Mann-Whitney U test showed that the IgG anti-CD25 antibody level was significantly higher in the patient group than the control group (P < 0.001) while the IgA antibody level was not significantly different between these two groups (P = 0.361). Spearman correlation analysis failed to reveal a significant correlation between the levels of anti-CD25 IgG and IgA antibodies in either the patient group (r = -0.027, P = 0.797, n = 94) or the control group (r = 0.055, P = 0.429, n = 209). The sensitivity against >90 % specificity was 37.2 % for the IgG assay with an inter-assay deviation of 9.4 %, and 8.2 % for the IgA assay with an inter-assay deviation of 13.0 %. Based on a cut-off value determined by the 99th percentile of control IgG levels, the positive rate was 7.4 % in patients with ESCC, in which patients at stage I had the highest positivity (11.5 %) (χ 2 = 11.10, P = 0.001, OR = 12.12, 95 % CI 1.93-75.94). Conclusions: This work suggests that circulating IgG autoantibody to CD25 may be a potential biomarker for early diagnosis of esophageal cancer. © 2013 Federación de Sociedades Españolas de Oncología (FESEO).


Huangfu M.,Jilin University | Xu S.,Jilin University | Li S.,Jilin University | Sun B.,Tumor Hospital of Jilin Province | And 3 more authors.
Tumor Biology | Year: 2016

The study was designed to test whether circulating autoantibodies against associated antigens (TAAs) were altered in early cervical cancer and benign cervical tumors. A total of 111 cervical cancer patients, 137 cervical benign tumor patients, and 160 healthy volunteers matched in age were recruited in this study. The expression of autoantibodies was tested using in-house developed enzyme-linked immunosorbent assay (ELISA) with linear peptide envelope antigens derived from TAAs. One-way ANOVA test showed that there was no difference in the CD25 autoantibody expression among the cervical cancer group, benign tumor group, and healthy control group (P = 0.063; P = 0.191). The expression of autoantibodies against survivin and TP53 in the cervical cancer group was significantly higher than that in the benign tumor group (P < 0.001; P < 0.001). The levels of autoantibodies against cyclinB-1 and ANXA-1 were higher in the cervical cancer group than in the healthy control group (P = 0.010; P = 0.001), while autoantibodies in the cervical cancer group showed no difference in expression compared with that in the benign tumor group. The panel of five TAAs showed a sensitivity of 37.8 % and a specificity of 90 %, which was much higher than the sensitivity of the single-TAA testing group. The data from this study further support our previous hypothesis that the detection of autoantibodies for the diagnosis of a specific cancer type can be enhanced using a panel of several selected TAAs as target antigens. © 2016 International Society of Oncology and BioMarkers (ISOBM)


PubMed | Jilin University, Pei Ling Guan Si Hospital and Tumor Hospital of Jilin Province
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2016

The study was designed to test whether circulating autoantibodies against associated antigens (TAAs) were altered in early cervical cancer and benign cervical tumors. A total of 111 cervical cancer patients, 137 cervical benign tumor patients, and 160 healthy volunteers matched in age were recruited in this study. The expression of autoantibodies was tested using in-house developed enzyme-linked immunosorbent assay (ELISA) with linear peptide envelope antigens derived from TAAs. One-way ANOVA test showed that there was no difference in the CD25 autoantibody expression among the cervical cancer group, benign tumor group, and healthy control group (P=0.063; P=0.191). The expression of autoantibodies against survivin and TP53 in the cervical cancer group was significantly higher than that in the benign tumor group (P<0.001; P<0.001). The levels of autoantibodies against cyclinB-1 and ANXA-1 were higher in the cervical cancer group than in the healthy control group (P=0.010; P=0.001), while autoantibodies in the cervical cancer group showed no difference in expression compared with that in the benign tumor group. The panel of five TAAs showed a sensitivity of 37.8% and a specificity of 90%, which was much higher than the sensitivity of the single-TAA testing group. The data from this study further support our previous hypothesis that the detection of autoantibodies for the diagnosis of a specific cancer type can be enhanced using a panel of several selected TAAs as target antigens.


PubMed | Jilin University, Pei Ling Guan Si Hospital and Tumor Hospital of Jilin Province
Type: Journal Article | Journal: International journal of clinical oncology | Year: 2015

Overexpression of tumor-associated antigens has been reported in many types of cancer and may trigger secretion of their autoantibodies. The present work was designed to test whether circulating antibody to FOXP3 protein-derived antigens was altered in early cervical cancer and cervical benign tumors.A total of 141 patients with cervical cancer, 133 patients with cervical benign tumors and 148 healthy age-matched volunteers were recruited. The level of circulating anti-FOXP3 IgG antibody was tested using an enzyme-linked immunosorbent assay developed in-house with linear peptide antigens derived from FOXP3 protein. The linear peptide antigens were designed according to the computational prediction of HLA-II epitopes.Students t test showed that anti-FOXP3 IgG in the malignant tumor group and the benign tumor group was significantly higher than in the control group (t = 6.127, p < 0.001; t = 2.704, p = 0.007). In addition, patients with stage I cervical cancer (t = 2.968, p = 0.003) had a significantly higher level of FOXP3 autoantibodies than patients with benign tumors. The sensitivity against >90 % specificity was 20.6 % with an interassay deviation of 11.7 % in the cervical cancer group. Based on a cut-off value determined by the 98th percentile of the control group IgG levels, the anti-FOXP3 IgG positivity was 2.1 % in patients with cervical cancer compared to 2.0 % in the health controls (chi-squared = 0.004, p = 0.952, OR = 1.051, 95 % CI 0.209-5.295).The circulating autoantibody to FOXP3 reflecting the continuous development of the cervical lesion, may be a potential biomarker with early prognostic values for cervical cancer.

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