Saccharomyces cerevisiae-like 1 overexpression is frequent in prostate cancer and has markedly different effects in Ets-related gene fusion-positive and fusion-negative cancers.

Abstract

The cytosolic factor Saccharomyces cerevisiae-like 1 (SEC14L1) is a regulator of lipid metabolism and signaling pathways that has been suggested to play a role in cancer. To learn more about its relevance for prostate cancer, SEC14L1 expression was analyzed on a tissue microarray containing samples from 11152 prostate cancer patients. In benign prostate glands, SEC14L1 immunostaining was absent or weak. In prostate cancer, SEC14L1 positivity was found in 80% of 9876 interpretable tumors including 9% with strong, 38% with moderate, and 32% with weak immunostaining. SEC14L1 expression was more frequent in Transmembrane Protease, Serine 2 (TMPRSS2):Ets-related gene (ERG) fusion-positive (89%) than in TMPSSR2:ERG-negative cancers (73%, P < .0001). Comparative analysis of SEC14L1 expression in TMPSSR2:ERG-positive and -negative cancers suggested a different role of SEC14L1 in the 2 subsets: in TMPSSR2:ERG-negative cancers, strong SEC14L1 expression was associated with early prostate-specific antigen recurrence (P = .0270), advanced tumor stage (P = .0042), high Gleason score (P < .0001), and high preoperative prostate-specific antigen levels (P = .0035). In TMPSSR2:ERG-positive cancers, strong SEC14L1 staining was linked to a prolonged recurrence-free interval (P = .0023) and absence of lymph node metastases (P = .0002). Strong associations of high SEC14L1 levels with chromosomal deletions (5q, 6q, phosphatase and tensin homolog gene, 3p13; P < .0001) and a high Ki-67 labeling index (P < .0001) were seen in TMPSSR2:ERG-negative but not TMPSSR2:ERG-positive cancers. A direct or indirect role of SEC14L1 in maintenance of genomic integrity and regulating cell proliferation may thus exclusively exist in TMPSSR2:ERG-negative cancers. In conclusion, our data suggest a markedly different role of SEC14L1 in TMPSSR2:ERG-negative and TMPSSR2:ERG-positive prostate cancers.

• Authors: Christoph Burdelski, Ysé Barreau, Ronald Simon, Claudia Hube-Magg, Sarah Minner, Christina Koop, Markus Graefen, Hans Heinzer, Guido Sauter, Corinna Wittmer, Stefan Steurer, Meike Adam, Hartwig Huland, Thorsten Schlomm, Maria Christina Tsourlakis, Alexander Quaas
• Journal: Human pathology (Hum Pathol) Vol. 46 Issue 4 Pg. 514-23 (Apr 2015) ISSN: 1532-8392 [Electronic] United States
• PMID: 25701228 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Carrier Proteins
• Oncogene Proteins, Fusion
• SEC14L1 protein, human
• TMPRSS2-ERG fusion protein, human
• Prostate-Specific Antigen

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics, metabolism)
• Carrier Proteins (metabolism)
• Humans
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Oncogene Proteins, Fusion (metabolism)
• Prognosis
• Prostate-Specific Antigen (genetics, metabolism)
• Prostatic Neoplasms (genetics, metabolism, pathology)
• Tissue Array Analysis (methods)
• Young Adult