Anti-ACY1 monoclonal antibody, clone FQS9556

Human aminoacylase-1 (N-acyl-L-amino-acid amidohydrolase, EC 3.5.1.14; ACY1) is a homodimeric zinc-binding enzyme that catalyzes the hydrolysis of N(alpha)-acylated amino acids. ACY1 has been assigned to chromosome 3p21.1, a region reduced to homozygosity in small cell lung cancer (SCLC), and has been reported to exhibit reduced or absent expression in SCLC cell lines and tumors. Two human cDNA libraries and one human genomic DNA library were screened with a previously isolated partial ACY1 cDNA to isolate a full-length transcript. Sequence analysis of clones from each of these libraries resulted in an ACY1 cDNA of 1438 base pairs with an open reading frame of 1224-base pairs coding for a putative protein of 408 amino acids with a predicted molecular mass of 45,882 Da. Sequence analysis revealed no homologies to previously reported cDNA or protein sequences and establishes ACY1 as the first member of a new family of zinc-binding enzymes to be so characterized. The subcellular location of ACY1 has been established as cytosolic by flow cytometry. Southern and northern analyses of ACY1 in SCLC cell lines failed to demonstrate any gross abnormalities of the ACY1 structural gene or instances of absent or aberrantly sized mRNA, respectively.

Background: Differential diagnosis of high-grade dysplastic nodules (HGDN) and well-differentiated hepatocellular carcinoma (WDHCC) represents a challenge to experienced hepatic clinicians, radiologists and hepatopathologists. Methods: The expression profiles of aminoacylase-1 (ACY1), sequestosome-1 (SQSTM1) and glypican-3 (GPC3) in low-grade dysplastic nodules (LGDN), HGDN and WDHCC were assessed by immunohistochemistry. The differential diagnostic performances of these three markers alone and in combination for HGDN and WDHCC were investigated by logistic regression models (HGDN = 21; WDHCC = 32) and validated in an independent test set (HGDN, n = 21; WDHCC n = 24). Postoperative overall survival and time to recurrence were evaluated by univariate and multivariate analyses in an independent set of 500 patients. Results: ACY1, SQSTM1 and GPC3 were differentially expressed in each group. For the differential diagnosis of WDHCC from HGDN, the sensitivity and specificity of the combination of ACY1 + SQSTM1 + GPC3 for detecting WDHCC were 93.8% and 95.2% respectively in the training set, which were higher than any of the three two-marker combinations. The validities of the four diagnostic models were further confirmed in an independent test set, and corresponding good sensitivity and specificity were observed. Interestingly, GPC3 expression in HCC tissues combined with serum a-fetoprotein (AFP) was found to be an independent predictor for overall survival and time to recurrence. Conclusions: ACY1 + SQSTM1 + GPC3 combination represents a potentially valuable biomarker for distinguishing between WDHCC and HGDN using immunohistochemistry. Meanwhile, low GPC3 staining combined with positive serum AFP may play a practical role in predicting poor postoperative outcome and high tumor recurrence risk.