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

Hum Pathol. 2015 Apr;46(4):514-23. doi: 10.1016/j.humpath.2014.06.006. Epub 2014 Jun 26.

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.

Keywords: Prognosis; Prostate cancer; SEC14L1; TMPSSR2:ERG; Tissue microarray.

MeSH terms

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

Substances

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