T2E ( TMPRSS2-ERG ) fusion transcripts are associated with higher levels of AMACR mRNA and a subsequent prostate cancer diagnosis in patients with atypical small acinar proliferation

Eryılmaz, Işıl Ezgi; Kordan, Yakup; Vuruşkan, Berna Aytaç; Kaygısız, Onur; Tunca, Berrin; Çeçener, Gülşah

doi:10.1016/j.gene.2017.12.038

Cited by 2 publications

(7 citation statements)

References 30 publications

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“…First, we detected T2E fusion transcript expression in 34.5% ( n = 19) of ASAP‐diagnosed Turkish patients by using RT‐qPCR, which was a higher rate than the rates reported in IHC‐based studies previously . Moreover, T2E fusion positivity was determined as significantly associated with a subsequent PC diagnosis in patients diagnosed with ASAP with a prebiopsy PSA level of 4‐10 ng/mL verifying our previous results . We also analyzed AMACR and AR expressions at transcriptional level in this study.…”

Section: Discussionsupporting

confidence: 83%

“…15,16 Moreover, T2E fusion positivity was determined as significantly associated with a subsequent PC diagnosis in patients diagnosed with ASAP with a prebiopsy PSA level of 4-10 ng/mL verifying our previous results. 28 We also analyzed AMACR and AR expressions at transcriptional level in this study. In the literature, diagnostic utility of AMACR has been suggested in diagnostically challenging prostatic tissue samples due to altered expression in PC, and due to high specificity and sensitivity at both the transcriptional and translational level.…”

Section: Discussionmentioning

confidence: 99%

“…In the literature, diagnostic utility of AMACR has been suggested in diagnostically challenging prostatic tissue samples due to altered expression in PC, and due to high specificity and sensitivity at both the transcriptional and translational level. 28,36,[38][39][40][41][42][43][44][45][46] AMACR expression at the RNA level, but not at the protein level, was also reported to be a predictive marker for PC risk in tissue samples of the patients with negative biopsies. 47 We emphasized in detail that the expression of AMACR should be assessed at the mRNA level, due to RNA/protein discordancy, when evaluating PC risk in biopsy samples.…”

Section: Discussionmentioning

confidence: 99%

“…We previously analyzed T2E and AMACR expression levels in ASAP-diagnosed patients with widely ranging PSA levels. 28 The results demonstrated that T2E expression was correlated with higher AMACR mRNA levels and could predict a subsequent PC diagnosis in ASAP-diagnosed patients with a PSA level of 4-10 ng/mL. Clinical implications of other PC-related RNA or protein markers in patients diagnosed with ASAP have not been investigated.…”

Section: Introductionmentioning

confidence: 95%

“…None of the PC‐related RNA markers have been analyzed at the transcriptional level in patients with ASAP prior to our first study. We previously analyzed T2E and AMACR expression levels in ASAP‐diagnosed patients with widely ranging PSA levels . The results demonstrated that T2E expression was correlated with higher AMACR mRNA levels and could predict a subsequent PC diagnosis in ASAP‐diagnosed patients with a PSA level of 4‐10 ng/mL.…”

Section: Introductionmentioning

confidence: 99%

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RNA‐based markers in biopsy cores with atypical small acinar proliferation: Predictive effect of T2E fusion positivity and MMP‐2 upregulation for a subsequent prostate cancer diagnosis

et al. 2018

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Background Atypical small acinar proliferation (ASAP) is a precursor lesion of prostate cancer (PC), and PC develops from this suspicious focus or an unsampled malignant gland nearby. However, PC‐related molecular alterations that could guide the timing of repeat biopsies and help monitor PC risk in ASAP‐diagnosed patients have not been investigated. The purpose of this study was to first investigate the expression of seven different PC‐related RNAs that included serine 2 (TMPRSS2): erythroblastosis virus E26 oncogene homolog (ERG) gene (TMPRSS2‐ERG, T2E) fusion, alpha‐methylacyl‐CoA racemase (AMACR), kallikrein related peptidase 3 (KLK3), androgen receptor (AR), prostate cancer specific antigen 3 (PCA3), and matrix metalloproteinases (MMP)‐2 and 9. Methods PC‐related RNAs were evaluated using a real‐time quantitative reverse transcription polymerase chain reaction (RT‐qPCR) system in pathologically ASAP‐diagnosed prostate biopsy cores from 55 patients presenting with a normal digital rectal examination and a PSA level of 4‐10 ng/mL. Results We detected that positive T2E fusion status (P = 0.013) and the expression of AMACR (P = 0.016), AR (P = 0.016) and MMP‐2 (P = 0.013) were independently and significantly associated with PC risk in ASAP patients. There were also several statistically significant correlations between expression levels. Additionally, we demonstrated that T2E fusion positive ASAP patients with higher MMP‐2 expression were more likely to be diagnosed with PC at a subsequent biopsy during the follow‐up period (P = 0.003). Conclusions Although, more clinical validations are needed for the stratification of PC risk in ASAP‐diagnosed biopsy cores, our current results indicate that the coexistence of T2E fusion positivity with MMP‐2 upregulation may help clinicians adjust their biopsy timetable and/or assessment of PC risk in ASAP‐diagnosed patients with a PSA level of 4‐10 ng/mL.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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RNA‐based markers in biopsy cores with atypical small acinar proliferation: Predictive effect of T2E fusion positivity and MMP‐2 upregulation for a subsequent prostate cancer diagnosis

et al. 2018

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Individualized detection of TMPRSS2-ERG fusion status in prostate cancer: a rank-based qualitative transcriptome signature

Li,

Su,

Liu

et al. 2024

World J Surg Onc

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Background TMPRSS2-ERG (T2E) fusion is highly related to aggressive clinical features in prostate cancer (PC), which guides individual therapy. However, current fusion prediction tools lacked enough accuracy and biomarkers were unable to be applied to individuals across different platforms due to their quantitative nature. This study aims to identify a transcriptome signature to detect the T2E fusion status of PC at the individual level. Methods Based on 272 high-throughput mRNA expression profiles from the Sboner dataset, we developed a rank-based algorithm to identify a qualitative signature to detect T2E fusion in PC. The signature was validated in 1223 samples from three external datasets (Setlur, Clarissa, and TCGA). Results A signature, composed of five mRNAs coupled to ERG (five ERG-mRNA pairs, 5-ERG-mRPs), was developed to distinguish T2E fusion status in PC. 5-ERG-mRPs reached 84.56% accuracy in Sboner dataset, which was verified in Setlur dataset (n = 455, accuracy = 82.20%) and Clarissa dataset (n = 118, accuracy = 81.36%). Besides, for 495 samples from TCGA, two subtypes classified by 5-ERG-mRPs showed a higher level of significance in various T2E fusion features than subtypes obtained through current fusion prediction tools, such as STAR-Fusion. Conclusions Overall, 5-ERG-mRPs can robustly detect T2E fusion in PC at the individual level, which can be used on any gene measurement platform without specific normalization procedures. Hence, 5-ERG-mRPs may serve as an auxiliary tool for PC patient management.

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T2E ( TMPRSS2-ERG ) fusion transcripts are associated with higher levels of AMACR mRNA and a subsequent prostate cancer diagnosis in patients with atypical small acinar proliferation

Cited by 2 publications

References 30 publications

RNA‐based markers in biopsy cores with atypical small acinar proliferation: Predictive effect of T2E fusion positivity and MMP‐2 upregulation for a subsequent prostate cancer diagnosis

RNA‐based markers in biopsy cores with atypical small acinar proliferation: Predictive effect of T2E fusion positivity and MMP‐2 upregulation for a subsequent prostate cancer diagnosis

Individualized detection of TMPRSS2-ERG fusion status in prostate cancer: a rank-based qualitative transcriptome signature

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