Development of autoantibody signatures for common cancers

Kobayashi, Makoto; Katayama, Hiroyuki; Fahrmann, Johannes F.; Hanash, Samir M.

doi:10.1016/j.smim.2020.101388

Cited by 25 publications

(27 citation statements)

References 103 publications

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“…Additionally, TA autoantibodies are more stable in vitro than other protein biomarkers, which facilitates their detection. Because of these advantages, TA autoantibodies are emerging as strong candidates for clinically useful cancer biomarkers [18]. However, TA autoantibody's diagnostic efficacy is often very low, limiting the development of relevant diagnostics.…”

Section: Introductionmentioning

confidence: 99%

Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma

Heo

Hwang

Lim

et al. 2020

IJMS

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Tumor-associated (TA) autoantibodies have been identified at the early tumor stage before developing clinical symptoms, which holds hope for early cancer diagnosis. We identified a TA autoantibody from HBx-transgenic (HBx-tg) hepatocellular carcinoma (HCC) model mouse, characterized its target antigen, and examined its relationship to human HCC. The mimotopes corresponding to the antigenic epitope of TA autoantibody were screened from a random cyclic peptide library and used for the detection of serum TA autoantibody. The target antigen of the TA autoantibody was identified as an oncogenic bi-functional purine biosynthesis protein, ATIC. It was upregulated in liver cancer tissues of HBx-tg mouse as well as human HCC tissues. Over-expressed ATIC was also secreted extracellularly via the cancer-derived exosomes, which might cause auto-immune responses. The cyclic peptide mimotope with a high affinity to anti-ATIC autoantibody, CLPSWFHRC, distinguishes between serum samples from HCC patients and healthy subjects with 70.83% sensitivity, 90.68% specificity (AUC = 0.87). However, the recombinant human ATIC protein showed a low affinity to anti-ATIC autoantibody, which may be incompatible as a capture antigen for serum TA autoantibody. This study indicates that anti-ATIC autoantibody can be a potential HCC-associated serum biomarker and suggests that autoantibody biomarker’s efficiency can be improved by using antigenic mimicry to native antigens present in vivo.

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Section: Introductionmentioning

confidence: 99%

Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma

Heo

Hwang

Lim

et al. 2020

IJMS

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“…Several approaches have been used to identify valuable TAAbs in cancers, among which serological analysis of expression cDNA libraries (SEREX) and serological proteome analysis (SERPA) are the most commonly used technologies (29)(30)(31). However, the false-positive rate of SEREX is too high, and the construction of a cDNA gene expression library from patients is time-consuming and unrepresentative.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Autoantibodies Based on the Human Proteomic Chips and Evaluation of Their Performance in the Detection of Gastric Cancer

et al. 2021

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Autoantibodies against tumor-associated antigens (TAAbs) can be used as potential biomarkers in the detection of cancer. Our study aims to identify novel TAAbs for gastric cancer (GC) based on human proteomic chips and construct a diagnostic model to distinguish GC from healthy controls (HCs) based on serum TAAbs. The human proteomic chips were used to screen the candidate TAAbs. Enzyme-linked immunosorbent assay (ELISA) was used to verify and validate the titer of the candidate TAAbs in the verification cohort (80 GC cases and 80 HCs) and validation cohort (192 GC cases, 128 benign gastric disease cases, and 192 HCs), respectively. Then, the diagnostic model was established by Logistic regression analysis based on OD values of candidate autoantibodies with diagnostic value. Eleven candidate TAAbs were identified, including autoantibodies against INPP5A, F8, NRAS, MFGE8, PTP4A1, RRAS2, RGS4, RHOG, SRARP, RAC1, and TMEM243 by proteomic chips. The titer of autoantibodies against INPP5A, F8, NRAS, MFGE8, PTP4A1, and RRAS2 were significantly higher in GC cases while the titer of autoantibodies against RGS4, RHOG, SRARP, RAC1, and TMEM243 showed no difference in the verification group. Next, six potential TAAbs were validated in the validation cohort. The titer of autoantibodies against F8, NRAS, MFGE8, RRAS2, and PTP4A1 was significantly higher in GC cases. Finally, an optimal prediction model with four TAAbs (anti-NRAS, anti-MFGE8, anti-PTP4A1, and anti-RRAS2) showed an optimal diagnostic performance of GC with AUC of 0.87 in the training group and 0.83 in the testing group. The proteomic chip approach is a feasible method to identify TAAbs for the detection of cancer. Moreover, the panel consisting of anti-NRAS, anti-MFGE8, anti-PTP4A1, and anti-RRAS2 may be useful to distinguish GC cases from HCs.

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“…There are a multitude of strategies available for discovery of tumor antigens directed autoantibodies in circulation. Each strategy targets a different repertoire of antigens and presents both advantages and disadvantages as we have previously outlined in a review [21]. The primary intent of this study is to explore the relationship of the autoantibody response in ovarian cancer to pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…The combined performance of these three markers resulted in an AUC of 0.9576 ( Figure 1C). Released antigens may occur in circulation bound to Ig [15,[19][20][21]. We profiled ovarian cancer circulating Ig-bound proteins in ovarian cancer subjects compared to controls using tandem mass tag (TMT)-based liquid chromatography mass spectrometry (LCMS).…”

Section: Recombinant Protein Array-based Ovarian Cancer Autoantibody mentioning

confidence: 99%

Proteome Profiling Uncovers an Autoimmune Response Signature That Reflects Ovarian Cancer Pathogenesis

Kobayashi

Katayama

Irajizad

et al. 2020

Cancers

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Harnessing the immune response to tumor antigens in the form of autoantibodies, which occurs early during tumor development, has relevance to the detection of cancer at early stages. We conducted an initial screen of antigens associated with an autoantibody response in serous ovarian cancer using recombinant protein arrays. The top 25 recombinants that exhibited increased reactivity with cases compared to controls revealed TP53 and MYC, which are ovarian cancer driver genes, as major network nodes. A mass spectrometry based independent analysis of circulating immunoglobulin (Ig)-bound proteins in ovarian cancer and of ovarian cancer cell surface MHC-II bound peptides also revealed a TP53–MYC related network of antigens. Our findings support the occurrence of a humoral immune response to antigens linked to ovarian cancer driver genes that may have utility for early detection applications.

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Development of autoantibody signatures for common cancers

Cited by 25 publications

References 103 publications

Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma

Cyclic Peptide Mimotopes for the Detection of Serum Anti–ATIC Autoantibody Biomarker in Hepato-Cellular Carcinoma

Identification of Novel Autoantibodies Based on the Human Proteomic Chips and Evaluation of Their Performance in the Detection of Gastric Cancer

Proteome Profiling Uncovers an Autoimmune Response Signature That Reflects Ovarian Cancer Pathogenesis

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