Systematic review: Tumor-associated antigen autoantibodies and ovarian cancer early detection

Fortner, Renée T.; Damms-Machado, Antje; Kaaks, Rudolf

doi:10.1016/j.ygyno.2017.07.138

Cited by 54 publications

(49 citation statements)

References 58 publications

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“…In serum samples predating symptomatic diagnosis by less than 6 months, each individual AAb marker showed a diagnostic sensitivity of around 0.20 at 0.98 specificity (SE98), similar to levels of diagnostic sensitivity observed in cross-sectional comparisons between clinically diagnosed ovarian cancer patients and cancer-free controls 9 . However, the ability of these AAb markers to distinguish cases from controls declined rapidly with time between blood draw and diagnosis, and SE98 estimates were close to zero in serum samples collected at greater than 1-year lead times.…”

Section: Discussionsupporting

confidence: 67%

“…Elevated serum P53 AAbs are observed in relation to several selected cancer types, including lung, breast and gastro-intestinal tumors 6–8 , and elevated AAb titers to P53 have also been observed in more than ten studies comparing ovarian cancer patients to cancer-free control subjects (reviewed in 9 ). Generally, the studies on ovarian cancer reported higher prevalence of elevated P53 AAbs among patients with high-grade serous tumors, as compared to other tumor subtypes, as was also observed in the current study.…”

Section: Discussionmentioning

confidence: 99%

“…The higher sensitivity and specificity of P53 AAb for high-grade serous tumors is likely related to the uniform occurrence of P53 mutations, with dysregulated P53 protein levels, in high-grade serous tumors. Like the P53 AAbs, elevated titers of AAbs to the cancer-testis antigens CTAG1A (NY-ESO-1) and CTAG2 (ESO2) have been observed in relation to a wide variety of cancer types 6–814, 15 , including ovarian cancer 20913 , and are likely related to the generally less differentiated nature of cancer cells, with aberrant expression of proteins that normally are expressed only in embryonic tissue types. AAbs to NUDT11 were first discovered as ovarian autoantigens through our own immuno-proteomic screening of ovarian cancer patients and controls 18 .…”

Section: Discussionmentioning

confidence: 99%

“…To date, more than 80 AAbs have been investigated for ovarian cancer detection 9 . In our own work, we have successfully discovered first sets of AAbs with high tumor specificity among ovarian cancer patients 10–12 .…”

Section: Introductionmentioning

confidence: 99%

“…Among these, antibodies against p53, the cancer/testis antigen CTAG-2 (also known as ESO2), and NUDT11 stood out as AAb markers with highest diagnostic sensitivity (up to 27.3 and 36.4%, respectively for serous tumors) at ≥97% specificity. A further AAb frequently reported to be associated with ovarian cancer 139 and other tumors types 14, 15 , is CTAG1A (also known as NY-ESO-01). However, with the exception of two recent studies on AAbs against MUC1 (Ca15.3) 16 and p53 17 , the early detection potential of tumor associated AAbs for ovarian cancer has been insufficiently evaluated in prospective cohort studies based on pre-diagnostic serum samples, and it is still unclear whether elevated AAb levels can be used to reliably detect ovarian cancer ahead of usual diagnosis.…”

Section: Introductionmentioning

confidence: 99%

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Tumor‐associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation

Kaaks

Fortner

Hüsing

et al. 2018

Intl Journal of Cancer

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Immuno-proteomic screening has identified several tumor-associated autoantibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer-testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs has been insufficiently explored in prospective studies. We performed ELISA measurements of AAbs to CTAG1A, CTAG2, P53 and NUDT11 proteins, for 194 patients with ovarian cancer and 705 matched controls from the European EPIC cohort, using serum samples collected up to 36 months prior to diagnosis under usual care. CA125 was measured using electrochemo-luminiscence. Diagnostic discrimination statistics were calculated by strata of lead-time between blood collection and diagnosis. With lead times ≤6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0.08-0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10-0.44] for P53 (0.33 [0.11-0.68] for high-grade serous tumors). However, at longer lead-times, the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01-0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tumor‐associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation

Kaaks

Fortner

Hüsing

et al. 2018

Intl Journal of Cancer

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Human epididymis protein 4 antigen‐autoantibody complexes complement cancer antigen 125 for detecting early‐stage ovarian cancer

Yang

Lü

Guo

et al. 2019

Cancer

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BACKGROUND: Early detection of ovarian cancer could significantly improve patient outcomes. Cancer antigen 125 (CA 125) is elevated in sera from approximately 60% of patients with early-stage (I/II) disease. Sensitivity might be improved through the combination of CA 125 with other biomarkers. Among potential biomarkers, antigen-autoantibody (Ag-AAb) complexes have received relatively little attention. METHODS: Luminex-based immunoassays were used to measure human epididymis protein 4 (HE4), anti-HE4 autoantibody, and HE4 Ag-AAb complexes in sera from patients with early-(n = 73) and late-stage ovarian cancers (n = 49) at the time of diagnosis and from asymptomatic women with (n = 15) or without ovarian cancer (n = 212) enrolled in the Normal Risk Ovarian Cancer Screening Study. RESULTS: At 98% specificity for healthy, asymptomatic women, 7% of patients with early-stage (I/II) ovarian cancer and 4% of patients with late-stage (III/IV) disease had elevated levels of HE4 autoantibody, whereas elevated levels of HE4 Ag-AAb complexes were detected in sera from 38% of early-stage cases and 31% of late-stage cases. Complementarity was observed in receiver operating characteristic (ROC) curves between HE4 Ag-AAb complexes and CA 125 levels in early-stage ovarian cancer (P < .001). CA 125 detected 63% of cases, and a combination of CA 125 and HE4 Ag-AAb complexes detected 81%. Complementarity was also observed in ROC curves for an independent validation set with 69 early-stage patients (P = .039). HE4 Ag-AAb complexes were detected in serial preclinical serum samples from women destined to develop ovarian cancer: they correlated with CA 125 but did not provide a lead time. CONCLUSIONS: HE4 Ag-AAb complexes could complement CA 125 in detecting a higher fraction of early-stage ovarian cancers. Cancer 2020;126:725-736.

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Seven tumor‐associated autoantibodies as a serum biomarker for primary screening of early‐stage non‐small cell lung cancer

Chen

Lü

Chen

2021

Clinical Laboratory Analysis

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Objective The purpose of this study was to analyze the levels of tumor‐associated autoantibodies (TAAbs) in lung diseases and determine their diagnostic efficiency in early‐stage non‐small cell lung cancer (NSCLC). Methods We retrospectively analyzed the levels of 7‐TAAbs in 177 newly diagnosed early‐stage NSCLC patients, 202 patients with lung benign diseases and 137 healthy cases. The levels of a panel of 7‐TAAbs, including p53, GAGE7, PGP9.5, CAGE, MAGE A1, SOX2, GBU4‐5, were measured by ELISA. Results The serum levels of p53, GAGE7, PGP9.5, CAGE, MAGE A1, SOX2, and GBU4‐5 were not statistically different among NSCLC, benign and healthy groups (p > 0.05). The area under the curve (AUC) of 7‐TAAbs was all lower than 0.70. The sensitivity of combined detection was the highest (23.73%), while the specificity was the lowest (88.79%). The positive rates of PGP9.5, SOX2, and combined detection were significantly different among the three groups (p < 0.05). Among them, PGP9.5 and combined detection were significantly different between the NSCLC and benign groups (p < 0.05), PGP9.5, SOX2 and combined detection were significantly different between the NSCLC and healthy groups (p < 0.05). Conclusions The diagnostic efficiency of 7‐TAAbs in early‐stage NSCLC was not high, so it cannot be used alone as a screening method for NSCLC.

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Systematic review: Tumor-associated antigen autoantibodies and ovarian cancer early detection

Cited by 54 publications

References 58 publications

Tumor‐associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation

Tumor‐associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation

Human epididymis protein 4 antigen‐autoantibody complexes complement cancer antigen 125 for detecting early‐stage ovarian cancer

Seven tumor‐associated autoantibodies as a serum biomarker for primary screening of early‐stage non‐small cell lung cancer

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