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

Kobayashi, Makoto; Katayama, Hiroyuki; Irajizad, Ehsan; Vykoukal, Jody; Fahrmann, Johannes F.; Kundnani, Deepali L.; Yu, Chuan; Cai, Yining; Hsiao, Fu Chung; Yang, Wei-Lei; Lü, Zhen; Celestino, Joseph; Long, James P.; Ann, Kim; Lu, Karen H.; Ladd, Jon J.; Urban, Nicole; Bast, Robert C.; Hanash, Samir M.

doi:10.3390/cancers12020485

Cited by 9 publications

(7 citation statements)

References 47 publications

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“…In a screening involving 20 ovarian cancer patients and 17 controls, circulating auto-antibodies towards P53 and MYC were primarily found, followed by other proteins of the P53 and MYC networks both by a recombinant protein-based assay and by an immunoglobulin-bound protein assay [ 103 ]. A study reported by Yang et al [ 104 ] also focused on P53 auto-antibodies.…”

Section: Cancer Auto-antibodiesmentioning

confidence: 99%

Anti-Cancer Auto-Antibodies: Roles, Applications and Open Issues

Jonge

Iamele

Maggi

et al. 2021

Cancers

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Auto-antibodies are classically associated with autoimmune diseases, where they are an integral part of diagnostic panels. However, recent evidence is accumulating on the presence of auto-antibodies against single or selected panels of auto-antigens in many types of cancer. Auto-antibodies might initially represent an epiphenomenon derived from the inflammatory environment induced by the tumor. However, their effect on tumor evolution can be crucial, as is discussed in this paper. It has been demonstrated that some of these auto-antibodies can be used for early detection and cancer staging, as well as for monitoring of cancer regression during treatment and follow up. Interestingly, certain auto-antibodies were found to promote cancer progression and metastasis, while others contribute to the body’s defense against it. Moreover, auto-antibodies are of a polyclonal nature, which means that often several antibodies are involved in the response to a single tumor antigen. Dissection of these antibody specificities is now possible, allowing their identification at the genetic, structural, and epitope levels. In this review, we report the evidence available on the presence of auto-antibodies in the main cancer types and discuss some of the open issues that still need to be addressed by the research community.

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Section: Cancer Auto-antibodiesmentioning

confidence: 99%

Anti-Cancer Auto-Antibodies: Roles, Applications and Open Issues

Jonge

Iamele

Maggi

et al. 2021

Cancers

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“…Yang et al showed that in advanced EOC patients, p53-AAbs levels can be elevated 8 months prior to CA125 and 22 months prior to clinical diagnosis in patients who do not experience a rise in CA125, emphasizing the importance of p53 as a marker that could complement CA125 at the time of diagnosis [ 176 ]. Three other studies showed a potential for p53 AAbs for early EOC diagnosis [ 185 , 186 , 187 ]. However, data from a study involving 194 women with OC that aimed to estimate the diagnostic capacity of p53 AAbs for invasive EOC, indicated that the added value of p53-AAbs as a marker for early detection of OC is still limited [ 188 ].…”

Section: The Role Of P53 In Hgsc Microenvironmentmentioning

confidence: 99%

Mutated p53 in HGSC—From a Common Mutation to a Target for Therapy

Saleh

Perets

2021

Cancers

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Mutations in tumor suppressor gene TP53, encoding for the p53 protein, are the most ubiquitous genetic variation in human ovarian HGSC, the most prevalent and lethal histologic subtype of epithelial ovarian cancer (EOC). The majority of TP53 mutations are missense mutations, leading to loss of tumor suppressive function of p53 and gain of new oncogenic functions. This review presents the clinical relevance of TP53 mutations in HGSC, elaborating on several recently identified upstream regulators of mutant p53 that control its expression and downstream target genes that mediate its roles in the disease. TP53 mutations are the earliest genetic alterations during HGSC pathogenesis, and we summarize current information related to p53 function in the pathogenesis of HGSC. The role of p53 is cell autonomous, and in the interaction between cancer cells and its microenvironment. We discuss the reduction in p53 expression levels in tumor associated fibroblasts that promotes cancer progression, and the role of mutated p53 in the interaction between the tumor and its microenvironment. Lastly, we discuss the potential of TP53 mutations to serve as diagnostic biomarkers and detail some more advanced efforts to use mutated p53 as a therapeutic target in HGSC.

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“…There is currently substantial interest in liquid biopsy approaches for cancer screening whether in a general population setting or for subjects at increased risk. A wide range of blood-based biomarkers are currently being investigated including circulating tumor DNA (ctDNA) representing mutations or altered methylation patterns; RNA, proteins, metabolites, autoantibodies to tumor antigens; exosomes; and circulating tumor cells [15][16][17][18][19][20] . Performance requirements depend on subjects' risk, with a need for very high specificity for subjects at average risk.…”

Section: Introductionmentioning

confidence: 99%