Tumor autoantibodies as biomarkers for predicting ovarian cancer recurrence

Abstract

Ovarian cancer (OVCA) has a high incidence of recurrence and a high rate of mortality. We performed a pilot study to evaluate the usefulness of tumor autoantibodies to tumor associated antigens (TAA) to predict OVCA recurrence. A validation study with 56 antigens, previously identified in the initial phase of the study, along with 13 known tumor antigens on protein arrays was performed on an independent cohort of recurrent and non-recurrent OVCA patients. Statistical analyses revealed that a panel of 3 antigens predicted recurrence at a median time of 9.07 months prior to clinical recurrence in a study population, where majority of patients had CA125 values less than 35 U/ml, with an average sensitivity, specificity and accuracy of 94.7%, 86.7% and 93.3% respectively. One of the top 3 antigens has been associated with the development of polymyositis (PM) which has been shown in some cases to precede the occurrence of ovarian carcinoma. Our results indicate that these 3 antigens have potential for predicting recurrence at an early time and may have better prognostic utility than CA125 alone for early therapeutic intervention. These biomarkers could guide us to identify those patients that could benefit most from maintenance or consolidation therapy.

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

“…Samples were collected and processed using the procedure as described earlier [5]. The demographics of patients in the training set were also described in earlier studies [5].…”

“…These autoantibodies to tumor associated antigens (TAAs) arise due to the generation of humoral immune response before evidence of clinical symptoms in cancer patients [5,7,8]. Our previous study indicated that a 3 biomarker panel, one being a peptide epitope from a known paraneoplastic antigen, predicted ovarian cancer recurrence at a median lead time of 9.07 months with 94.7% sensitivity, 86.7% specificity, and 93.3% accuracy, in a cohort of ovarian cancer patients where normalization of CA125 had occurred after the surgery and completion of chemotherapy [5]. Paraneoplastic antigens can elicit a humoral immune response in cancer patients as these antigens are expressed in the cells of nervous system and tumor [24].…”

Colorectal Cancer Circulating Biomarkers

“…In ovarian cancer, Tainsky lab detected recurrences at 9.07 months prior to clinical recurrence (Chatterjee et al 2012). They demonstrated that 3 out of 56 antigens displayed in phages and printed in microarrays correctly classified recurrent and nonrecurrent ovarian cancer patients (Chatterjee et al 2012). …”

“…Correlation values were calculated for all pairs of TAAs identified through protein microarrays (Babel et al 2009;Barderas et al 2013) or phage microarrays (Babel et al 2011 treatment with neoadjuvant chemotherapy (Anderson et al 2008). In ovarian cancer, Tainsky lab detected recurrences at 9.07 months prior to clinical recurrence (Chatterjee et al 2012). They demonstrated that 3 out of 56 antigens displayed in phages and printed in microarrays correctly classified recurrent and nonrecurrent ovarian cancer patients (Chatterjee et al 2012).…”

“…A variant of SEREX, where phages are printed on a microarray format, has been also tested for autoantibody discovery in a high-throughput version (Wang et al 2005;Chatterjee et al 2006;Babel et al 2011;Chatterjee et al 2012). Here, TAA discovery takes advantage on the multiplexing analysis of both T7 phages and microarrays (Fig.…”