Novel Biomarkers for Prostate Cancer Including Noncoding Transcripts

Abstract

Levels of 27 transcripts were investigated as potential novel markers for prostate cancer, including genes encoding plasma membrane proteins (ADAM2, ELOVL5, MARCKSL1, RAMP1, TMEM30A, and TMEM66); secreted proteins (SPON2, TMEM30A, TMEM66, and truncated TMEFF2 (called POP4)); intracellular proteins (CAMK2N1, DHCR24, GLO1, NGFRAP1, PGK1, PSMA7, SBDS, and YWHAQ); and noncoding transcripts (POP1 (100 kb) from mRNA AK000023), POP2 (4 kb from mRNA AL832227), POP3 (50 kb from EST CFI40309), POP5 (intron of NCAM2, accession DO668384), POP6 (intron of FHIT), POP7 (intron of TNFAIP8), POP8 (intron of EFNA5), POP9 (intron of DSTN), POP10 (intron of ADAM2, accession DO668396), POP11 (87kb from EST BG194644), and POP12 (intron of EST BQ226050)). Expression of POP3 was prostate specific, whereas ADAM2, POP1, POP4, POP10, ELOVL5, RAMP1, and SPON2 had limited tissue expression. ELOVL5, MARCKSL1, NGFRAP1, PGK1, POP2, POP5, POP8, PSMA7, RAMP1, and SPON2 were significantly differentially expressed between laser microdissected malignant versus benign clinical samples of prostate tissue. PGK1, POP2, and POP12 correlated to clinical parameters. Levels of CAMK2N1, GLO1, SDBS, and TMEM30A transcripts tended to be increased in primary prostate cancer from patients who later had biochemical failure. Expression of GLO1, DHCR24, NGFRAP1, KLK3, and RAMP1 were significantly decreased in metastatic castration-recurrent disease compared with androgen-dependent primary prostate cancer. These novel potential biomarkers may therefore be useful in the diagnosis/prognosis of prostate cancer.

Store-operated Ca2+ Entry-associated Regulatory factor (SARAF) Plays an Important Role in the Regulation of Arachidonate-regulated Ca2+ (ARC) Channels

“…Using biotinylation analysis we detected SARAF expressed in the PM, which is consistent with the suggested location of the product of TMEM66 in prostate cancer cells (18). Furthermore, we have found that SARAF in the PM is able to associate with Orai1 and this interaction is enhanced by stimulation with AA.…”

“…As depicted in Fig. 2B (17); however, the product of TMEM66, the former name of the gene encoding SARAF, has been suggested to be located in the PM (18). Since ARC channels consist of a heteropentameric complex of three Orai1 and two Orai3 subunits with the participation of PM-resident STIM1 (4 -5) we investigated whether there is a pool of SARAF constitutively expressed in the PM and whether SARAF interacts with ARC channels.…”

Differential upregulation of the hypothetical transmembrane protein 66 (TMEM66) in multiple sclerosis patients with potential inflammatory response

“…In other studies, the TMEM66 gene was expressed among different novel androgen-responsive genes in prostate cancer. Those genes were indicated to play a role in the molecular mechanisms of androgen-dependency of the prostate and were also considered as targets for therapy or biomarkers of prostate cancer (29,30).…”

Expression of Tumor Necrosis Factor-alpha-induced Protein 8 in Pancreas Tissues and its Correlation with Epithelial Growth Factor Receptor Levels

“…The early studies had showed that TNFAIP8 is an oncogenic factor that may play a role in tumor progression, and exogenous expression of TNFAIP8 enhances cell survival. proliferation and inhibition of activities of the apoptotic enzymes caspase 8 and caspase 3 (You et al, 2001;Romanuik et al, 2009). Human breast cancer cells transfected with TNFAIP8 increased proliferation, cell migration, and tumor growth rate (Kumar et al, 2004).…”