Abstract A010: ANO7 expression changes in prostate cancer progression — Association with an aggressive phenotype?

Abstract

Abstract Introduction The expression level and single nucleotide polymorphisms of the prostate-specific gene ANO7 have been shown to correlate with prostate cancer (PrCa) outcome. Very little is known about ANO7, apart from its expression profile in tissues and that the protein is either a calcium-activated ion channel or a lipid scramblase. Our results suggest that ANO7 likely has a role in PrCa progression and that loss of ANO7 is associated with malignant PrCa. Materials and methods Sections of a prostate cancer formalin-fixed paraffin-embedded tissue microarray were used for ANO7 mRNA and protein detection. mRNA was detected with fluorescent in situ hybridization (FISH). Protein was detected with immunohistochemistry (IHC) using a polyclonal anti-ANO7 antibody (HPA035730). mRNA from fresh radical prostatectomy primary tumor samples were sequenced and subsequent gene expression levels were analyzed for co-expression with ANO7. The sample set consisted of a matched tumor and benign tissue sample (15+15) from each patient. Results The FISH images indicated explicitly that ANO7 mRNA is exclusively expressed in the luminal cells of the prostatic glandular epithelium. ANO7 mRNA is expressed in all cancerous lumina-forming glandular structures, but not in poorly-formed glands or sheets of cancer, in which ANO7 mRNA expression is very low or non-existent. Morphologically benign glands amidst cancerous tissue showed no expression, in contrast to tissue in which benign glands are predominating. The IHC showed a similar staining pattern to FISH.ANO7 co-expression gene set enrichment analysis resulted in 19 positively correlating and 77 negatively correlating pathways in KEGG (Kyoto Encyclopedia of Genes and Genomes) terms. Most of the positively correlating terms relate to metabolism, whereas among the negatively correlating terms, there were many signal transduction and cell growth and death-related pathways, such as Hippo, Ras, and p53 signaling pathways. Conclusions ANO7 mRNA and protein expression correlate spatially in the tissue, showing that the expression is specific to differentiated luminal cells and highly reduced in high-grade cancer. This notion is supported by the co-expressed gene-set enrichment analysis, which is showing a negative correlation of ANO7 with many pathways that are associated with aggressive PrCa. Mainly metabolism-related processes were positively correlated with ANO7, which could indicate that ANO7 is linked to the reprogramming of metabolism in the cells during cancer progression. Further research aims to identify the pathways in which ANO7 plays a significant role and to elucidate how the ANO7 protein functionally alters signaling related to PrCa progression. Citation Format: Olli Metsälä, Gudrun Wahlström, Pekka Taimen, Johanna Schleutker. ANO7 expression changes in prostate cancer progression — Association with an aggressive phenotype? [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A010.