Can serum autoantibodies be a potential early detection biomarker for breast cancer in women? A diagnostic test accuracy review and meta-analysis

Abstract

Background The increasing incidence of breast cancer necessitates the need to explore alternate screening strategies that circumvent the setbacks of conventional techniques especially among population that report earlier age at diagnosis. Serum autoantibodies is one such potential area of interest. However, their ubiquitous presence across cancer types limits its applicability to any one specific type of cancer. This review was therefore carried out to explore and consolidate available evidence on autoantibodies for early detection of breast cancer and to identify those that demonstrated a higher sensitivity. Methods A diagnostic test accuracy (DTA) review was carried out to ascertain serum autoantibodies that could be used for early detection of breast cancer among women. All relevant articles that investigated the role of autoantibodies in early detection of breast cancer were included for the review. MEDLINE, Scopus, ProQuest, Ovid SP, and Cochrane Library were searched extensively for eligible studies. Quality of the included studies was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. RevMan 5.3 was used for exploratory and MetaDTA 2019 for hierarchical analyses. The review helped identify the most frequently investigated autoantibodies and a meta-analysis further consolidated the findings. Results A total of 53 articles were included for the final analysis that reported over a 100 autoantibodies that were studied for early detection of breast cancer in women. P53, MUC1, HER2, HSP60, P16, Cyclin B1, and c-Myc were the most frequently investigated autoantibodies. Of these P53, MUC1, HER2, and HSP60 exhibited higher summary sensitivity measures. While the individual pooled sensitivity estimates ranged between 10 and 56%, the panel sensitivity values reported across studies were higher with an estimated range of 60–87%. Conclusion Findings from the review indicate a higher sensitivity for an autoantibody panel in comparison to individual assays. A panel comprising of P53, MUC1, HER2, and HSP60 autoantibodies has the potential to be investigated as an early detection biomarker for breast cancer.

Circulating Proteins as Diagnostic Biomarkers in Breast Cancer

“…Many analyses have shown that practically all tumors leak their constituents into the bloodstream; so, blood may be utilized to examine biomolecules derived from tumors [8]. Researches have concentrated on blood-based biomarkers, such as proteins reviewed previously as well as listed in table 1, which are less intrusive, convenient to determine routinely, and appear to be an option for BC screening [9,10]. -Thioredoxin 1 (Trx1): Trx1 regulates transcription factor DNA binding activity, which is crucial for cancer cell growth [23].…”

“…-ITGA2B (integrin subunit alpha IIb), FLNA (Filamin A), RAP1A (Ras-associated protein-1A), TLN-1 (Talin-1): Previous researches have demonstrated that a individual tumormarker frequently fails to capture sensitivity and specificity in determining a specific malignancy, which can be raised in both normal people and in benign diseases. As a result, a collection of biomarkers was evaluated in order to identify the panel with the greatest accuracy in early identifying BC patients from women without cancer [10]. In Claudia Fredolini et al study, affinity hydrogel nanoparticles coupled with LC-MS/MS analysis was deployed to measure low abundance proteins in serum samples from invasive ductal carcinoma (IDC) patients.…”

A Luminex Approach to Develop an Anti-Tumor-Associated Antigen Autoantibody Panel for the Detection of Prostate Cancer in Racially/Ethnically Diverse Populations

“…Moreover, the anti-HSP60 autoantibody has been reported in the serum of cancer patients and can be used as a diagnostic biomarker [ 32 ]. For instance, the presence of this autoantibody has been reported in patients with hepatocellular carcinoma [ 8 , 33 ], breast cancer [ 16 ], ovarian cancer [ 34 ], and colorectal cancer [ 35 ]. In this study, we found 41.8% (38/91) of PCa patients tested positive for the anti-HSP60 autoantibody with a moderate diagnostic performance (AUC = 0.868).…”

“…We have also reported significantly higher levels of autoantibodies to p53, ENO1, and BIRC5 in patients with PCa compared to healthy controls [ 13 , 14 ]. In particular, autoantibodies to p53, p16, and p62 were widely detected in multiple tumors [ 15 , 16 , 17 , 18 ]. Additionally, other autoantibodies targeting SOX2, HIF1-α, NY-ESO-1/CTAG1B, MUC1, Her2, GAL1, and GAL3 have been frequently identified in cancer patients [ 16 , 18 , 19 , 20 , 21 , 22 ].…”

“…In particular, autoantibodies to p53, p16, and p62 were widely detected in multiple tumors [ 15 , 16 , 17 , 18 ]. Additionally, other autoantibodies targeting SOX2, HIF1-α, NY-ESO-1/CTAG1B, MUC1, Her2, GAL1, and GAL3 have been frequently identified in cancer patients [ 16 , 18 , 19 , 20 , 21 , 22 ]. Given the high number of human cancers in which these autoantibodies are expressed, we have termed these autoantibodies “common cancer-associated autoantibodies (CAAs)”.…”