Identification of a New Panel of Serum Autoantibodies Associated with the Presence of In situ Carcinoma of the Breast in Younger Women

Abstract

Purpose: We examined the feasibility of using a panel of autoantibodies to multiple tumor-associated proteins as a method for early detection of breast cancer and, more particularly, carcinoma in situ (CIS). Experimental Design: PPIA, PRDX2, and FKBP52 were identified as early-stage breast cancer autoantigens by proteomic approaches. The seroreactivity of a panel of antibodies consisting of these three antigens and two previously described autoantigens, HSP60 and MUC1, was tested on 235 samples (60 from primary breast cancer patients, 82 from CIS patients, and 93 from healthy controls) with the use of specific ELISAs. FKBP52, PPIA, and PRDX2 mRNA and protein expression levels were evaluated by reverse transcription-PCR and immunohistochemistry in early-stage breast tumors. Results: Three of five autoantibodies, FKBP52, PPIA, and PRDX2, showed significantly increased reactivity in primary breast cancer and CIS compared with healthy controls.When combined, the five markers significantly discriminated primary breast cancer [receiver operating characteristic area under the curve, 0.73; 95% confidence interval (95% CI), 0.60-0.79] and CIS (receiver operating characteristic area under the curve, 0.80; 95% CI, 0.71-0.85) from healthy individuals. Importantly, the receiver operating characteristic^area under the curve value of the autoantibody panel was able to distinguish CIS, including high grades, from healthy controls in women under the age of 50 years (receiver operating characteristic area under the curve, 0.85; 95% CI, 0.61-0.92). Finally, only FKBP52 mRNA and protein levels were found to be increased in CIS and primary breast cancer compared with healthy breast tissue. Conclusions: This autoantibody assay against a panel of five antigens allows for an accurate discrimination between early-stage breast cancer, especially CIS, and healthy individuals. These results could be of interest in detecting early breast cancer as an aid to mammography, especially in women under the age of 50 years with aggressive cancers.

Downregulation of FKBP14 by RNA interference inhibits the proliferation, adhesion and invasion of gastric cancer cells

“…FKBP14 belongs to the FKBP family, which perform important biological functions in the cell. Several members of the FKBP family are established to contribute to carcinogenesis, including FKBP12 (5,6), FKBP65 (7) and FKBP52 (8)(9)(10), while other FKBPs are downregulated in human cancer, including FKBP38 (11). However, the functions of FKBP14 in human cancer remain to be elucidated.…”

“…FKBP65 expression was increased in early benign lesions compared with normal mucosa (7). FKBP52 has been demonstrated to be overexpressed in breast (8), prostate (9) and hepatocellular carcinoma tissues (10). FKBP38 has also been found to be selectively downregulated in aggressive types of schwannoma tumor cell lines (11).…”

Development of Autoantibody Signatures as Biomarkers for Early Detection of Colorectal Carcinoma

“…Autoantibodies to known or unknown tumor-associated antigens (TAA) are present in sera of patients with some malignancies (7)(8)(9)(10)(11)(12)(13)(14). Various technologies such as serologic analysis of recombinant cDNA expression libraries (SEREX), phage display, and protein arrays have been used to identify autoantibody signatures for cancer diagnosis (14)(15)(16)(17)(18)(19).…”

The Role of Peptidyl Prolyl Isomerases in Aging and Vascular Diseases

“…Moreover, FKBP52 is highly expressed in hormone-positive cancers such as oestrogen receptor positive (ER+) breast cancer; its expression in pre-invasive breast cancer was also much higher than the surrounding normal breast tissue speculating its role in breast cancer initiation 180,181 . FKBP52 is not a functional regulator of the oestrogen receptor but interestingly, it is upregulated in breast tumours and FKBP52 gene methylation only occurs in ER negative breast cancer cells 182 .…”