Utility of paraneoplastic antigens as biomarkers for surveillance and prediction of recurrence in ovarian cancer

Abstract

BACKGROUND Ovarian cancer is frequently diagnosed at an advanced stage and 70% of patients experience recurrence months to years from initial diagnosis. The expression of paraneoplastic antigens can result in the occurrence of onconeural autoantibodies in ovarian cancer that may be associated with neurological disorders that are clinically manifested in patients before diagnosis of ovarian cancer. These paraneoplastic antigens can serve as excellent biomarkers not only for early detection but also for monitoring ovarian cancer recurrence. OBJECTIVE To assess the immunoreactivity of our previous 3 biomarkers along with 3 paraneoplastic antigens, HARS, Ro52 and CDR2 for the evaluation of their sensitivity in predicting recurrence before the clinical relapse of the ovarian cancer. METHODS Western blot immunoassays were performed to assess the immunoreactivity of 6 antigens with 21 recurrent ovarian cancer patients. RESULTS The results indicated that antibodies to HARS, Ro52, CDR2 and 5H6 antigens predicted ovarian cancer recurrence 5.03 months before the clinical or symptomatic relapse in 21 ovarian cancer patients with a sensitivity of 90.5% when CA125 levels were below the standard cutoff (35 U/ml). CONCLUSION Our study suggests that appearance of onconeural antibodies prior to the rise in CA125 during post treatment surveillance can be a useful diagnostic to predict ovarian cancer recurrence.

B Cells as an Immune-Regulatory Signature in Ovarian Cancer

“…For example, a study by Wilson et al [31] in early-stage HGSC, found that AAbs against HSF1 detected early stage malignancy better than CA125 alone and that combined measurements of anti-HSF1, anti-CCDC155 and CA125 might be useful for detecting early stage HGSC, thus highlighting the potential role of AAb biomarkers in detection of early disease. Another study, by Chatterjee et al [32], suggested a role for AAbs in the surveillance of ovarian cancer and in predicting its recurrence, as AAbs to 5H6, HARS, CDR2 and Ro52 antigens predicted ovarian cancer recurrence 5.03 months before clinical onset in 21 patients, with a sensitivity of 90.5%. In contrast, levels of the known biomarker CA125 were below the standard cutoff (35 U/mL).…”

Reduced levels of actin gamma 1 predict poor prognosis in ovarian cancer patients

“…15,16 Early detection and effective treatment are key factors in controlling the occurrence and progression of this disease. [17][18][19] Despite surgery and chemotherapy being the main treatments for ovarian cancer, the 5-year survival rate for patients with advanced ovarian cancer remains at 20-25% due to extensive abdominal metastasis, surgical limitations and drug-resistant recurrence after chemotherapy. [20][21][22][23] Consequently, the identification of sensitive markers for ovarian cancer is an active area of research.…”

Role of biomarkers for early detection of ovarian cancer recurrence

“…However, it can occur also in the absence of paraneoplastic symptoms leading to their diagnostic utility in asymptomatic subjects. Chatterjee et al (14) have carried out a retrospective study in 21 ovarian cancer patients, to evaluate the sensitivity of a panel of 6 paraneoplastic antigens (HARS, CDR2, Ro52, 4B7, 4H4 and 5H6) to predict recurrence of ovarian cancer before the rise in CA125 level (cutoff 35 U/mL) or to the radiologic indication of clinical recurrence. The result of this study showed that antibodies to the 4 antigens, HARS, Ro52, CDR2 and 5H6, predicted ovarian cancer recurrence with a sensitivity of 90.5% when CA125 levels were below the standard cutoff (35 U/mL).…”

“…The result of this study showed that antibodies to the 4 antigens, HARS, Ro52, CDR2 and 5H6, predicted ovarian cancer recurrence with a sensitivity of 90.5% when CA125 levels were below the standard cutoff (35 U/mL). The average time for predicting recurrence obtained was 5.03 months before the clinical or symptomatic relapse (14). However, it must be emphasized that these markers have only been evaluated in a small number of patients in whom CA125 values are within the normal range.…”

“…In this way, biomarkers can be used not only as a diagnostic tool but also as a prognostic indicator that gives the estimate of disease recurrence and categorizes patients at different risk levels for specific outcomes (12). Nowadays, the clinical symptoms of relapse are determined by measuring the level of serum CA125, one of the most extensively used tumor biomarkers in standard clinical practice for disease surveillance (14). Levels of CA125 are correlated with response to treatment and it has been established that it can rise 4.8 months before clinical disease recurrence, providing time to pursue multiple courses of novel or conventional therapy (11), and a recent study showed, also a major benefit from early initiation of treatments (15).…”