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

Abstract

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.

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

“…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 ].…”

Early Detection of Ovarian Cancer

“…Kaaks, et al , performed a prospective analysis on a selected panel of four autoantibodies—against TP53, CTAG1A, CTAG2 and NUDT11— using serum samples collected up to 36 months before diagnosis from 194 ovarian cancer patients and 705 matched control participants 23 . With lead times less than or equal to 6 months, sensitivity for early detection ranged from 19–23% for the four autoantibodies at 98% specificity, but with lead time of greater than 1-year, sensitivity ranged from only 1–11%.…”

High-throughput assessment of the antibody profile in ovarian cancer ascitic fluids

“…In fact, after presenting an initial response, the majority of OC patients experience disease recurrence. 57,59 We showed an association between the TA antibody signature in ascites from Figure 6. Gene expression and OS correlation.…”

“…However, the added value of the selected TA antibodies as markers for the early detection of OC with the use of CA-125 remained limited. 23,57 Tumor antibodies in OC have been explored as biomarkers not only for early diagnosis but also for predicting prognosis and recurrence as well as developing therapeutic approaches. 58 The possibility of correlating the level of tumor autoantibodies with the clinical outcome of cancer patients might permit patient stratification into prognostic categories, which would help in the selection of second-line therapeutic treatments following primary debulking surgery and platinum-based firstline chemotherapy.…”