Detection of Early Cancer: Genetics or Immunology? Serum Autoantibody Profiles as Markers of Malignancy

Poletaev, Alexander B.; Pukhalenko, Alexander I.; Kukushkin, A.B.; Свиридов, П В

doi:10.2174/1871520615666150716105255

Cited by 16 publications

(16 citation statements)

References 27 publications

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“…In recent years, many discoveries of serum tumor biomarkers identified by genomic and proteomic techniques have been documented, such as miRNAs [ 22 ], Long noncoding RNAs [ 23 ], Circulating tumor DNAs [ 24 ], circulating tumor cells [ 25 ], and metabolites [ 26 ]. However, few of these biomarkers for early cancer detection have surpassed blinded Phase III validation studies and have been applied to the clinic over the past two decades [ 11 , 27 , 28 ]. Accumulating evidence of circulating serum autoantibodies in cancer patients highlighted the potential use of autoantibody in early detection [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…Autoantibodies against tumor-associated antigens (TAAs) were initially identified in the sera of melanoma patients in 1977 [ 8 ], and have drawn significant attention as they have created chances to develop a source of biomarkers based on the immune system and could be detected at early onset of the cancer disease. Over the past two decades, many studies have demonstrated the potential utility of autoantibodies for cancer lies in the role of early detection, which might supplement current screening strategies to aid early cancer diagnosis [ 9 – 11 ]. However, the relationship between sera autoantibodies and EJA has not been well characterized.…”

Section: Introductionmentioning

confidence: 99%

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Combined detection of serum autoantibodies as diagnostic biomarkers in esophagogastric junction adenocarcinoma

Chen

Guo

et al. 2018

Gastric Cancer

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Background We previously found that autoantibodies against a panel of six tumor-associated antigens (p53, NY-ESO-1, MMP-7, Hsp70, PRDX6 and Bmi-1) may aid in early detection of esophageal squamous cell carcinoma. Here we aimed to evaluate the diagnostic value of this autoantibody panel in esophagogastric junction adenocarcinoma (EJA) patients. Methods Serum autoantibody levels were measured by enzyme-linked immunosorbent assay in a training cohort and a validation cohort. We used receiver-operating characteristics (ROC) to calculate diagnostic accuracy. Results We recruited 169 normal controls and 122 EJA patients to the training cohort, and 80 normal controls and 70 EJA patients to the validation cohort. Detection of the autoantibody panel demonstrated an area under the curve (AUC) of 0.818, sensitivity 59.0% and specificity 90.5% in training cohort, and AUC 0.815, sensitivity 61.4% and specificity 90.0% in validation cohort in the diagnosis of EJA. Measurement of the autoantibody panel could distinguish early stage EJA patients from normal controls (AUC 0.786 and 0.786, sensitivity 50.0% and 56.0%, and specificity 90.5% and 90.0%, for training and validation cohorts, respectively). Moreover, a restricted panel consisting of autoantibodies against p53, NY-ESO-1 and Bmi-1 exhibited similar diagnostic performance for EJA (AUC 0.814 and 0.823, sensitivity 53.5% and 60.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively) and early stage EJA (AUC 0.744 and 0.773, sensitivity 55.6% and 52.0%, and specificity 90.5% and 93.7%, for training and validation cohorts, respectively). Conclusions Autoantibodies against an optimized TAA panel as serum biomarkers appear to help identify the present of early stage EJA. Electronic supplementary material The online version of this article (10.1007/s10120-018-0894-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Combined detection of serum autoantibodies as diagnostic biomarkers in esophagogastric junction adenocarcinoma

Chen

Guo

et al. 2018

Gastric Cancer

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“…These antigens may trigger the immune system to produce high titers of autoantibodies or tumor-associated autoantibodies (TAABs). These TAABs can be promising biomarkers for early diagnosis of breast cancer based on concentration, which may precede clinical confirmation of cancer by months to years, as the detection of autoantibodies can be performed earlier than the originating tumor-associated antigens (TAAs) assays [ 2 , 32 , 33 ]. Moreover, there are a plethora of TAABs, which are highly stable in serum and whole-blood compared to other polypeptides [ 34 ].…”

Section: Autoantibodies In Breast Cancermentioning

confidence: 99%

Autoantibodies as Potential Biomarkers in Breast Cancer

et al. 2018

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Breast cancer is a major cause of mortality in women; however, technologies for early stage screening and diagnosis (e.g., mammography and other imaging technologies) are not optimal for the accurate detection of cancer. This creates demand for a more effective diagnostic means to replace or be complementary to existing technologies for early discovery of breast cancer. Cancer neoantigens could reflect tumorigenesis, but they are hardly detectable at the early stage. Autoantibodies, however, are biologically amplified and hence may be measurable early on, making them promising biomarkers to discriminate breast cancer from healthy tissue accurately. In this review, we summarized the recent findings of breast cancer specific antigens and autoantibodies, which may be useful in early detection, disease stratification, and monitoring of treatment responses of breast cancer.

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“…The quote and metaphor "an apple found in a car is not synonymous of proof that apples grow in cars" [18] by using an image ( Fig. 1) [18,19] illustrates why "genetic studies have not led to a breakthrough in either the diagnosis or the treatment of cancers" [20].…”

Section: Introductionmentioning

confidence: 99%

Prelude and premise to the special issue: disruption of homeostasis-induced signaling and crosstalk in the carcinogenesis paradigm “Epistemology of the origin of cancer”

Brücher

Jamall

2019

4open

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The vast majority of anticancer strategies are symptomatic but in order to achieve some tangible progress, we need to identify the cause(s) of the majority of cancers. There is a kind of zeitgeist that findings in genetics, namely somatic mutations, are reflexively viewed as being causative for carcinogenesis, although some 80% of all cancers are presently termed “sporadic” (i.e., with no proven cause). The observation that one inch of cancerous liver tissue can have more than 100 000 000 mutations and an identical mutation can result in different phenotypes, depending on the environment surrounding that mutation, makes it very unlikely that mutations by themselves are causative of most cancers. 4open debuts its Special Issue series with papers that provide strong evidence that carcinogenesis consists of a 6-step sequence (1) a pathogenic stimulus followed by (2) chronic inflammation from which develops (3) fibrosis with associated remodeling of the extracellular microenvironment, and from these changes a (4) precancerous niche (PCN), a product of fibrosis with remodeling by persistent inflammation develops which triggers the deployment of (5) a chronic stress escape strategy and when this fails to be resolved it results in (6) the normal cell to cancerous cell transition. This Special Issue contains separate papers discussing undervalued ubiquitous proteins, chronic inflammation, eicosanoids, microbiome and morbid obesity, PCN, cell transition, followed by altered signaling induced by Metformin, NF-κB signaling and crosstalk during carcinogenesis, and a brief synopsis. In essence, the available evidence, both in vitro and in vivo, lends credence to the proposition that the majority of cancers occur from a disruption of homeostasis-induced signaling and crosstalk in the carcinogenesis paradigm “Epistemology of the origin of cancer”.

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Detection of Early Cancer: Genetics or Immunology? Serum Autoantibody Profiles as Markers of Malignancy

Cited by 16 publications

References 27 publications

Combined detection of serum autoantibodies as diagnostic biomarkers in esophagogastric junction adenocarcinoma

Combined detection of serum autoantibodies as diagnostic biomarkers in esophagogastric junction adenocarcinoma

Autoantibodies as Potential Biomarkers in Breast Cancer

Prelude and premise to the special issue: disruption of homeostasis-induced signaling and crosstalk in the carcinogenesis paradigm “Epistemology of the origin of cancer”

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