Fatty Acid Binding Protein 7 Is a Molecular Marker in Adenoid Cystic Carcinoma of the Salivary Glands: Implications for Clinical Significance

Abstract

Adenoid cystic carcinoma (ACC) is an aggressive malignant neoplasm of the salivary glands. Its diagnosis is difficult due to overlapping features with other salivary tumors. Gene expression analysis may complement traditional diagnostic methods. We searched gene expression patterns in the Gene Expression Omnibus (GEO) database and in our tumor and normal samples. The biologic and prognostic potential of the identified genes was analyzed. The GEO data set of primary xenografted ACCs revealed that expression of five genes, engrailed homeobox 1 (EN1), fatty acid binding protein 7 (FABP7), hemoglobin epsilon 1, MYB, and versican (VCAN), was dramatically increased. mRNA expression of EN1, FABP7, MYB, and VCAN distinguished our sporadic ACCs from normal tissues and benign tumors. FABP7 expression appeared to be regulated differently from EN1 and MYB and was crossly correlated with poor prognosis in our ACC cohort. Immunohistochemistry showed that FABP7 protein was predominantly expressed in the nucleus of myoepithelial cells of both tubular and cribriform subtypes. In contrast, in the solid subtype, which is often associated with a lower survival rate, FABP7 protein was uniformly expressed in cancerous cells. One case with cribriform architecture and the highest level of FABP7 mRNA showed strong FABP7 staining in both duct-type epithelial and myoepithelial cells, suggesting that diffuse expression of FABP7 protein might be related to aggressive tumor behavior and poor prognosis. We propose FABP7 as a novel biomarker in ACC. The molecule may be useful in diagnosis and for identifying more effective therapies targeting this protein or upstream molecules that regulate it.

The value of MYB as a prognostic marker for adenoid cystic carcinoma: Meta‐analysis

“…Ten retrospective studies including 658 patients with ACC fulfilled the inclusion criteria and were included in this meta‐analysis (Figure ) . Three studies without outcome events were excluded, and one study that investigated the impact of MYB mRNA on prognosis was also excluded . The characteristics of the 10 eligible studies are provided in Table .…”

“…Roden et al employed a break‐apart FISH probe strategy, whereas West et al used a come‐together and break‐apart FISH probe strategy, with two probes flanking the MYB gene and one probe located at the 3′ end of the NFIB gene. Furthermore, some studies detected MYB‐NFIB fusion products by reverse‐transcriptase polymerase chain reaction, in which the primer design, positive cutoff, and multiplexing factors influenced assay outcomes . Brill et al found MYB‐NFIB fusion in 86% of ACCs using fresh frozen tissues, in contrast to 44% when using formalin‐fixed paraffin‐embedded tissues.…”

Clinical and molecular insights into adenoid cystic carcinoma: Neural crest‐like stemness as a target

“…Interestingly, FABP7 is a shared NOTCH1/SOX10 target that marks neural stem cells in the subventricular CNS zone, as well as CSC in glioblastoma . Fatty acid‐binding protein 7 is coexpressed with SOX10 in ACC and basal‐like breast cancers, and in these tumor types FABP7 expression serves as a diagnostic marker associated with poor prognosis . Although the mechanism of FABP7 activity in cancer or CSC maintenance is not well described, activation of FABP7 in cancers increases fatty acid uptake resulting in enhanced cell survival and protection against reactive oxygen species …”

NOTCH1 and SOX10 are Essential for Proliferation and Radiation Resistance of Cancer Stem–Like Cells in Adenoid Cystic Carcinoma

“…An important insight into this cooperation, which has not been previously appreciated, was provided by the co-expression of FABP7 that relied on both NOTCH1 and SOX10, and the role of FABP7 in regulating expression of genes critical for cell survival. FABP7 has been recently described as a novel diagnostic and prognostic ACC marker (48) and was also implicated in glioblastoma, melanoma, and basal-like breast cancer; however, its downstream targets and molecular mechanisms of activation have not been studied. Our data associate FABP7 with the expression of SKP2 and multiple other genes involved in survival, proliferation, and metabolic pathways pointing at a novel signaling pathway that stimulates CSC in ACC.…”