Discovery and Validation of Serum Autoantibodies Against Tumor-Associated Antigens as Biomarkers in Gastric Adenocarcinoma Based on the Focused Protein Arrays

Yang, Qian; Qin, Jiejie; Sun, Guiying; Qiu, Cuipeng; Jiang, Di; Ye, Hua; Xiao, Wang; Dai, Liping; Zhu, Jicun; Wang, Peng; Zhang, Jianying

doi:10.14309/ctg.0000000000000284

Cited by 12 publications

(7 citation statements)

References 41 publications

(25 reference statements)

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“…Early detection is one of the most promising approaches to improve clinical outcomes for patients with cancer. Considerable efforts have been made to develop more sensitive and specific tests to detect cancer with different combinations of autoantibodies (6,(26)(27)(28). Because of its high sensitivity to early gastric cancers, serum WT1-271 IgM antibody may be used as a detection marker in the screening of gastric cancer in combination with autoantibodies, especially in the early stages.…”

Section: Discussionmentioning

confidence: 99%

Serum WT1‑271 IgM antibody as a novel diagnostic marker for Gastric Cancer

et al. 2022

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The Wilms tumor 1 gene, WT1, is overexpressed in various types of cancer, including gastric cancer. The product of WT1 is highly immunogenic and is a promising target molecule for cancer immunotherapy. The current study aimed to examine the production of WT1-specific IgG and IgM autoantibodies to identify biomarkers of diagnostic value in patients with gastric cancer. IgG antibodies that bind to WT1-derived peptides were obtained, the serum levels of which correlate with those of IgG antibodies against the WT1 protein in patients with intestinal malignancies. The serum levels of IgG and IgM antibodies against the WT1-271 peptide (271-288 amino acids) were examined in 39 healthy individuals and 97 patients with gastric cancer. The positivity cutoff value was determined according to the receiver operating characteristic curve. The association between WT1-271 IgM and the clinicopathological factors and prognosis of patients was additionally analyzed. The results revealed that serum WT1-271 IgM antibody levels in patients with gastric cancer were significantly higher than those in healthy individuals. The sensitivity and specificity of this antibody for gastric cancer were 67.0 and 71.8%, respectively; this sensitivity was improved when compared with conventional tumor markers (P<0.001). There was no statistical difference in WT1-271 IgG antibody levels between patients with gastric cancer and healthy individuals. Serum WT1-271 IgM antibody levels were not significantly associated with clinicopathological factors but were associated with unfavorable prognosis. Serum WT1-271 IgM antibody levels could serve as a diagnostic biomarker in patients with gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Serum WT1‑271 IgM antibody as a novel diagnostic marker for Gastric Cancer

et al. 2022

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“…Most of the previous studies showed that combining multiple biomarkers can remarkably improve the diagnostic accuracy and speci city in different cancerous diseases, such as OC, BC, ESCC, gastric cancer (GC) and LC [17,[21][22][23][24][25]. Jiang et al utilized decision tree method to construct a diagnostic panel consist of seven TAAbs (TP53, NPM1, FGFR2, PIK3CA, GNA11, HIST1H3B, and TSC1) with the AUC of 0.897 and sensitivity and speci city of 94.4% and 84.9% [17].…”

Section: Discussionmentioning

confidence: 99%

Humoral immune response to tumor-associated antigen Ubiquilin 1 (UBQLN1) and its tumor-promoting potential in lung cancer

Wang

Ouyang

Liu

et al. 2022

Preprint

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Background The aim of this study is to investigate the expression of UBQLN1 in lung cancer (LC) tissue and the diagnostic capability of autoantibody to UBQLN1 (anti-UBQLN1) in the detection of LC, as well as discriminating malignant and benign pulmonary nodules (PNs). Methods Sera from 798 participants of three independent cohorts were used to discover and validate the level of autoantibodies via HuProt microarray and Enzyme-linked immunosorbent assay (ELISA). Logistic regression analysis was applied to establish model combining anti-UBQLN1, CT characteristics and traditional serum biomarkers. Receiver operating characteristic curve (ROC) analysis was performed to evaluate the diagnostic potential. Immunohistochemistry of tissue array was performed to detect UBQLN1 expression in 88 LC tissues and 88 para-tumor tissues. qRT-PCR and western blotting were performed to detect the expression of UBQLN1 at the mRNA and protein levels in cell lines, respectively. Trans-well assay and cell counting kit-8 (CCK-8) was used to investigate the functions of UBQLN1 in two lung cancer cell lines (CALU3 and H358). Results Anti-UBQLN1 was identified with the highest fold change by means of protein microarray in the discovery cohort. The level of anti-UBQLN1 in LC patients was obviously higher than that in NC or patients with benign lung disease of validation cohort 1 (P < 0.05). The area under the curve (AUC) of anti-UBQLN1 was 0.610 (95%CI: 0.508–0.713) while reached at 0.822 (95%CI: 0.784–0.897) when combining anti-UBQLN1with CEA, CYFRA21-1, CA125 and three CT indicators (vascular notch sign, lobulation sign and mediastinal lymph node enlargement) in the discrimination of malignant from benign PNs. UBQLN1 protein was overexpressed in lung adenocarcinoma (LUAD) tissues compared to para-tumor tissues. UBQLN1 knockdown remarkably inhibited the migration, invasion and proliferation of two lung cancer cell lines. Conclusions UBQLN1 can elicit the humoral immune response as tumor-associated antigen in LC. The autoantibody to UBQLN1 might be a potential biomarker for LC diagnosis and might be useful to improve the discrimination of malignant from benign PNs.

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“…Among them, WGCNA is an excellent algorithm in screening the biological markers, and it has been used in many studies 26 . The human proteomics chip contains 21 000 human recombinant proteins in this study, which can comprehensively screen TAAs 53‐56 . In summary, bioinformatics can screen for genes that play important roles in the occurrence and development of HCC.…”

Section: Discussionmentioning

confidence: 99%

“… 26 The human proteomics chip contains 21 000 human recombinant proteins in this study, which can comprehensively screen TAAs. 53 , 54 , 55 , 56 In summary, bioinformatics can screen for genes that play important roles in the occurrence and development of HCC. Hence, those two methods were used together to screen valuable TAAs as much as possible.…”

Section: Discussionmentioning

confidence: 99%

A novel immunodiagnosis panel for hepatocellular carcinoma based on bioinformatics and the autoantibody‐antigen system

Wang

Han

et al. 2021

Cancer Science

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Hepatocellular carcinoma (HCC) is a malignancy with a dismal survival rate. The novel autoantibodies panel may provide new insights for the diagnosis of HCC. Biomarkers screened by two methods (bioinformatics and the antigen‐antibody system) were taken as candidate tumor‐associated antigens (TAAs). Enzyme‐linked immunosorbent assay was used to detect the corresponding autoantibodies in 888 samples of verification and validation cohorts. The verification cohort was used to verify the autoantibodies. Samples in the validation cohort were randomly divided into a train set and a test set with the ratio of 6:4. A diagnostic model was established by support vector machines within the train set. The test set further verified the model. Eleven TAAs were selected (AAGAB, C17orf75, CDC37L1, DUSP6, EID3, PDIA2, RGS20, PCNA, TAF7L, TBC1D13, and ZIC2). The titer of six autoantibodies (PCNA, AAGAB, CDC37L1, TAF7L, DUSP6, and ZIC2) had a significant difference in any of the pairwise comparisons among the HCC, liver cirrhosis, and normal control groups. The titer of these autoantibodies had an increasing tendency. Finally, an optimum diagnostic model was constructed with the six autoantibodies. The AUCs were 0.826 in the train set and 0.773 in the test set. The area under the curve (AUC) of this panel for diagnosing early HCC was 0.889. The diagnostic ability of the panel reduced with the progress of HCC. The positive rate of the panel in diagnosing alpha‐fetoprotein (AFP)‐negative patients was 75.6%. For early HCC, the sensitivity of the combination of AFP with the panel was 90.9% and superior to 53.2% of AFP alone. The novel immunodiagnosis panel combining AFP may be a new approach for the diagnosis of HCC, especially for early‐HCC cases.

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Discovery and Validation of Serum Autoantibodies Against Tumor-Associated Antigens as Biomarkers in Gastric Adenocarcinoma Based on the Focused Protein Arrays

Cited by 12 publications

References 41 publications

Serum WT1‑271 IgM antibody as a novel diagnostic marker for Gastric Cancer

Serum WT1‑271 IgM antibody as a novel diagnostic marker for Gastric Cancer

Humoral immune response to tumor-associated antigen Ubiquilin 1 (UBQLN1) and its tumor-promoting potential in lung cancer

A novel immunodiagnosis panel for hepatocellular carcinoma based on bioinformatics and the autoantibody‐antigen system

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