Colorectal Cancer Circulating Biomarkers

Barderas, Rodrigo; Villar-Vázquez, Roi; Casal, J. Ignacio

doi:10.1007/978-94-007-7681-4_29

Cited by 4 publications

(4 citation statements)

References 69 publications

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“…One of the main advantages of this approach for cancer diagnosis is that antibodies are highly stable molecules with a long tradition in immunoassays, facilitating their standardization in serological assays. In the last years, the development of serologic screening of natural and/or recombinant protein microarrays has led to the discovery of hundreds of novel proteins target of autoantibodies in cancer patients 16,33–41 . As a discovery platform, these technologies hold the promise to complete the cancer autoantibody immunome once microarrays containing the total proteome become available (considering one canonical protein per gene) 34,42,43 .…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, the cancer humoral immune response is a polyclonal response, which recognizes linear and/or conformational immunogenic epitopes within the same protein 33–35,48,49 . In addition, recent advances in native protein display technologies suggest that conformational-dependent discontinuous epitopes may represent up to 90% of the total B-cell response and are often dependent on the secondary or tertiary structure of proteins 50 .…”

Section: Discussionmentioning

confidence: 99%

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The specific seroreactivity to ∆Np73 isoforms shows higher diagnostic ability in colorectal cancer patients than the canonical p73 protein

Garranzo‐Asensio

Guzmán-Aránguez

Povés

et al. 2019

Sci Rep

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The p53-family is tightly regulated at transcriptional level. Due to alternative splicing, up to 40 different theoretical proteoforms have been described for p73 and at least 20 and 10 for p53 and p63, respectively. However, only the canonical proteins have been evaluated as autoantibody targets in cancer patients for diagnosis. In this study, we have cloned and expressed in vitro the most upregulated proteoforms of p73, ΔNp73α and ΔNp73β, for the analysis of their seroreactivity by a developed luminescence based immunoassay test using 145 individual plasma from colorectal cancer, premalignant individuals and healthy controls. ∆Np73α seroreactivity showed the highest diagnostic ability to discriminate between groups. The combination of ∆Np73α, ∆Np73β and p73 proteoforms seroreactivity were able to improve their individual diagnostic ability. Competitive inhibition experiments further demonstrated the presence of unique specific epitopes in ΔNp73 isoforms not present in p73, with several colorectal patients showing unique and specific seroreactivity to the ΔNp73 proteoforms. Overall, we have increased the complexity of the humoral immune response to the p53-family in cancer patients, showing that the proteoforms derived from the alternative splicing of p73 possess a higher diagnostic ability than the canonical protein, which might be extensive for p53 and p63 proteins.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The specific seroreactivity to ∆Np73 isoforms shows higher diagnostic ability in colorectal cancer patients than the canonical p73 protein

Garranzo‐Asensio

Guzmán-Aránguez

Povés

et al. 2019

Sci Rep

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“…Up to date, CRC TAAs have been mainly identified through protein microarrays-based proteomic techniques such as natural and recombinant protein microarrays and phage microarrays [5,6]. Such techniques are mainly hindered by the limited identification of dysregulated proteins to those printed onto the array.…”

Section: Introductionmentioning

confidence: 99%

Identification of tumor-associated antigens with diagnostic ability of colorectal cancer by in-depth immunomic and seroproteomic analysis

Garranzo‐Asensio

Segundo‐Acosta

Povés

et al. 2020

Journal of Proteomics

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“…Previously, we and others have used different types and versions of high‐density protein microarrays (phage microarrays, glycopeptide microarrays, natural protein microarrays and recombinant ORFs protein microarrays) to characterize the CRC humoral response and several CRC TAAs have been described (for reviews see ). In addition, using CRC murine models we showed that autoantibody detection allows very early CRC diagnosis providing an effective demonstration that CRC TAAs can be used for cancer screening and preclinical diagnosis .…”

Section: Introductionmentioning

confidence: 99%

Development of a novel multiplex beads‐based assay for autoantibody detection for colorectal cancer diagnosis

et al. 2016

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Humoral response in cancer patients can be used for early cancer detection. By screening high-density protein microarrays with sera from colorectal cancer (CRC) patients and controls, we identified 16 tumor-associated antigens (TAAs) exhibiting high diagnostic value. This high number of TAAs requires the development of multiplex assays combining different antigens for a faster and more accurate prediction of CRC. Here, we have developed and optimized a bead-based assay using nine selected TAAs and two controls to provide a multiplex test for early CRC diagnosis. We screened a collection of 307 CRC patients' and control sera with the beads assay to identify and validate the best TAA combination for CRC detection. The multiplex bead-based assay exhibited a similar diagnostic performance to detect the humoral response in comparison to multiple ELISA analyses. After multivariate analysis, a panel composed of GTF2B, EDIL3, HCK, PIM1, STK4, and p53, together with gender and age, was identified as the best combination of TAAs for CRC diagnosis, achieving an AUC of 89.7%, with 66% sensitivity at 90.0% fixed specificity. The model was validated using bootstrapping analysis. In summary, we have developed a novel multiplex bead assay that after validation with a larger independent cohort of sera could be utilized in a high-throughput manner for population screening to facilitate the detection of early CRC patients.

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Colorectal Cancer Circulating Biomarkers

Cited by 4 publications

References 69 publications

The specific seroreactivity to ∆Np73 isoforms shows higher diagnostic ability in colorectal cancer patients than the canonical p73 protein

The specific seroreactivity to ∆Np73 isoforms shows higher diagnostic ability in colorectal cancer patients than the canonical p73 protein

Identification of tumor-associated antigens with diagnostic ability of colorectal cancer by in-depth immunomic and seroproteomic analysis

Development of a novel multiplex beads‐based assay for autoantibody detection for colorectal cancer diagnosis

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