PCA3

Summary

PCA3 (prostate cancer associated 3, HGNC:8637) is a long non-coding RNA gene on chromosome 9q21.2.

This gene produces a spliced, long non-coding RNA that is highly overexpressed in most types of prostate cancer cells and is used as a specific biomarker for this type of cancer. This gene is embedded in an intronic region of the prune2 gene on the opposite DNA strand. The transcript regulates prune2 levels through formation of a double-stranded RNA that undergoes adenosine deaminase acting on RNA-dependent adenosine-to-inosine RNA editing. In prostate cancer derived cells, overexpression of PCA induced downregulation of prune2, leading to decreased cell proliferation. Conversely, silencing in prostate cancer cells resulted in increased proliferation. Regulation of this gene appears to be sensitive to androgen-receptor activation, a molecular signature of prostate cancer. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 50652 — RefSeq curated summary.

At a glance

• Gene type: non-coding (lncRNA) — no protein product; not a drug target. Variant/disease associations are omitted (they would be positional, from an overlapping protein-coding gene).

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8637
Approved symbol	PCA3
Name	prostate cancer associated 3
Location	9q21.2
Locus type	RNA, long non-coding
Status	Approved
Aliases	DD3, NCRNA00019, PCAT3, PRUNE2-AS1
Ensembl gene	ENSG00000225937
Ensembl biotype	lncRNA
OMIM	604845
Entrez	50652
RNAcentral	URS00008E3A1F — lncRNA, 3757 nt, 1 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 18 lncRNA

ENST00000412654, ENST00000642205, ENST00000642542, ENST00000642794, ENST00000643823, ENST00000644302, ENST00000644657, ENST00000645196, ENST00000645704, ENST00000645809, ENST00000645839, ENST00000645887, ENST00000646854, ENST00000646947, ENST00000647300, ENST00000647325, ENST00000647409, ENST00000665558

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000412654 — 4 exons

Exon	Start	End
ENSE00001597304	76782668	76782832
ENSE00001664394	76784116	76787569
ENSE00001693743	76783705	76783887
ENSE00003825340	76764438	76764555

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 91.31.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0231 / max 36.9115, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97005	0.0231	3

Top tissues by expression

132 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	91.31	gold quality
corpus callosum	UBERON:0002336	88.88	gold quality
sural nerve	UBERON:0015488	87.87	gold quality
calcaneal tendon	UBERON:0003701	82.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.24	gold quality
popliteal artery	UBERON:0002250	81.16	gold quality
tibial artery	UBERON:0007610	81.09	gold quality
mucosa of stomach	UBERON:0001199	80.75	gold quality
thoracic aorta	UBERON:0001515	80.31	gold quality
ascending aorta	UBERON:0001496	80.13	gold quality
descending thoracic aorta	UBERON:0002345	79.33	gold quality
urinary bladder	UBERON:0001255	79.08	gold quality
lower esophagus muscularis layer	UBERON:0035833	78.87	gold quality
lower esophagus	UBERON:0013473	78.82	gold quality
muscle layer of sigmoid colon	UBERON:0035805	77.61	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	77.03	gold quality
right coronary artery	UBERON:0001625	74.37	gold quality
left coronary artery	UBERON:0001626	74.08	gold quality
skeletal muscle tissue	UBERON:0001134	73.58	gold quality
cerebellum	UBERON:0002037	72.13	gold quality
cerebellar cortex	UBERON:0002129	72.10	gold quality
myometrium	UBERON:0001296	71.92	gold quality
cerebellar hemisphere	UBERON:0002245	71.81	gold quality
prostate gland	UBERON:0002367	71.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.14	gold quality
prefrontal cortex	UBERON:0000451	71.10	gold quality
colon	UBERON:0001155	70.88	gold quality
right hemisphere of cerebellum	UBERON:0014890	70.69	gold quality
body of uterus	UBERON:0009853	69.94	gold quality
fundus of stomach	UBERON:0001160	69.56	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.12

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

• The only prostate specific region of DD3 is exon 4. (PMID:12680228)
• DD3 is the most prostate cancer-specific gene described so far. (PMID:12814669)
• Review. PCA3 is the most specific prostate malignancy marker. The gene has 4 distinct exons, causing a number of differently sized transcripts. The exons have an unusual number of stop codons. Its expression suggests a unique transcriptional regulation. (PMID:14607216)
• Up-regulation of IGFBP-3 gene expression is associated with Prostatic Neoplasms (PMID:15067329)
• PCA3 assay is insensitive to pre-analytical factors, performs well analytically and correctly classifies a high percent of subjects with known prostate cancer status (PMID:18061575)
• The PCA3 score was independent of the number of previous biopsies, age, prostate volume, and total PSA level. Moreover, the PCA3 score was significantly higher in men with high-grade prostate intraepithelial neoplasia versus those without HGPIN. (PMID:18602209)
• PCA3 mRNA was overexpressed in prostate cancer tissue. (PMID:18684556)
• Incorporation of prostate cancer gene 3 improved the diagnostic acuracy of the Prostate Cancer Prevention Trial risk calculator. (PMID:18707724)
• Upregulation of two new PCA3 isoforms in prostate cancer tissues (PMID:19319183)
• [Review] PCA3 is prostate-specific. The strong association between PCA3 mRNA overexpression and malignant transformation of prostate epithelium indicates its potential as a diagnostic biomarker. (PMID:19424173)
• Results indicated the clinical usefulness of the combination of DD3 and PSA as molecular markers in the early diagnosis of prostate cancer (PMID:19489685)
• In this patient cohort, no correlation is found between urinary PCA3 and the clinoco-pathological features of prostate cancer. The predictive value of PCA3 for the aggressiveness of prostate cancer cannot be confirmed in this study. (PMID:19708043)
• Despite the presence of the recently identified marginal PCA3 transcripts in human prostate cancer, the major PCA3 isoform still constitutes the best target for diagnostic purposes. (PMID:19760627)
• Increased expression of PCA3 is associated with prostate cancer. (PMID:20114043)
• High PCA3 expression is associated with prostate cancer progression. (PMID:20332487)
• The PCA3 value correlates with the probability of a positive prostate biopsy. The high negative predictive value can facilitate the decision for or against a prostate biopsy. (PMID:20424427)
• PCA3 as a first-line screening test shows improvement of the performance characteristics and identification of serious disease compared with PSA in this prescreened population (PMID:20637539)
• Adding PCA3 to the decision to biopsy or not resulted in detecting 64% additional cases of prostate cancer in men with PSA levels <3.0 ng/ml. (PMID:20933321)
• Both Chun’s nomogram and the PCPT calculator, by incorporating PCA3, can assist in the decision to biopsy by assignment of an individual risk of prostate cancer, specifically in the PSA levels <10 ng/ml. (PMID:20947244)
• PCA3 was confirmed as a valuable predictor of pathologically confirmed low-volume disease and insignificant prostate carcinoma. (PMID:20980098)
• The use of PCA3 in combination with serum PSA and other clinical information enhances the diagnostic accuracy of prostate cancer detection.[review] (PMID:21093148)
• Data indicate that PSA, PSMA, hK2, PSCA, DD3, and their combinations, combined analysis of PSA and/or hK2 expression in pelvic lymph nodes could predict biochemical recurrence free survival (BRFS) following radical prostatectomy (RP). (PMID:21600799)
• Data indicate combining serum PSA, PCA3, and TMPRSS2:ERG in a multivariable algorithm optimized for clinical utility improved cancer prediction. (PMID:21600800)
• presence of the (TAAA)n short tandem repeat polymorphisms in the PCA3 promoter region may be a risk factor for prostate cancer in the Chinese population (PMID:21655300)
• Chronic prostatitis does not influence urinary PCA3 score. (PMID:21761426)
• The association between the PCA3 score and prostate cancer aggressiveness needs further evaluation, the inclusion of the PCA3 score into patient management may provide clinicians with another tool to more accurately determine the course of treatment. (PMID:21883822)
• In the setting of prior negative biopsies, PCA3 was independently associated with prostate cancer in a multivariable model. (PMID:22042252)
• analysis of the accuracy of PCA3 and PSA in prostate cancer diagnosis at repeat saturation biopsy (PMID:22199313)
• The only 2 true prostate cancer specific biomarkers identified to date remain PCA3 and TMPRSS2:ERG gene fusion. (PMID:22245323)
• results suggest a link between PCA3 and metastatic prostate cancer; evaluation of individual genetic profiles according to the PCA3 -845 G>A polymorphism may elucidate the function of this gene and mechanisms involved in its regulation and role in prostat (PMID:22288776)
• PCA3 expression levels increase progressively in fused TMPRSS2:ERG gene samples from patients with benign prostatic hyperplasia to those with prostate cancer. (PMID:22674214)
• Data indicate that prostate Cancer Gene 3 (PCA3) score was highly specific and we specially recommend its use in patients with persistent elevated prostate specific antigen (PSA) and prior negative biopsies. (PMID:22687565)
• The PCA3 score did not show any significant correlation with tumor volume, primary or secondary Gleason pattern-specific tumor volumes in prostate cancer patients. (PMID:22782916)
• PCA3 score is useful in preoperative staging of a single microfocus of prostate cancer diagnosed at saturation biopsy (PMID:22868485)
• Non-coding RNA PCA3 has a significant positive correlation with PRUNE2 and may play an important role in the pathogenesis of leiomyosarcoma. (PMID:22967466)
• Our findings suggest that the ncRNA PCA3 is involved in the control of prostate cancer cell survival (PMID:23130941)
• PCA3 and Phi were superior to the other evaluated parameters but their combination gave only moderate enhancements in diagnostic accuracy for PCa at first or repeat prostate biopsy (PMID:23213079)
• The measurement of PCA3 mRNA in post-prostatic massage urine was a reasonable diagnostic test for prostate cancer with acceptable sensitivity and high specificity (PMID:23223645)
• Of the 10 target genes, PCA3 and PSCA mRNAs were significantly differently expressed in cancerous tissue than in histologically benign tissue of cancerous prostates (PMID:23391636)
• PCA3 human molecular urine test is a good indicator for prostate biopsy repeat in patients with prostate cancer. (PMID:23416644)

Cross-species orthologs

0 orthologs

Protein

Non-coding RNA — no protein product; not a drug target.

Function

No curated pathway, Gene-Ontology, or interaction data.

Disease & clinical

No curated disease, variant, or cancer-driver associations.

Drugs & pharmacology

No drug or pharmacology data — not an established drug target.