SnoN overexpression is predictive of poor survival in patients with esophageal squamous cell carcinoma

Ann Surg Oncol. 2008 Oct;15(10):2965-75. doi: 10.1245/s10434-008-9986-y. Epub 2008 Jul 9.

Abstract

Background: Earlier studies have identified the minimal overlapping region of amplification at 3q26 in esophageal squamous cell carcinoma (ESCC) by comparative genomic hybridization (CGH) analysis. These include PIK3CA which encodes the p110alpha catalytic subunit of phosphatidylinositol (PI) 3-kinase, a telomerase RNA component (TERC), a squamous cell carcinoma-related oncogene (SCCRO), ecotropic viral integration site-1 (EVI-1), and a Ski-related novel oncogene (SnoN). In the present study, we investigated the mRNA levels of four candidate genes (TERC, SCCRO, EVI-1, and SnoN) to determine whether genes other than PIK3CA are targets for amplification at 3q26 in ESCC. And also, we examined SnoN expression in ESCC samples.

Methods: Fifty-nine representative cases with ESCC were selected from our archives. We performed quantitative RT-PCR of four candidate genes (TERC, SCCRO, EVI-1, and SnoN) and immunohistochemistry for SnoN. Finally, we correlated these findings with the clinicopathological characteristics to determine their interrelationship.

Results: Among the four genes we tested, only SnoN mRNA was consistently overexpressed in primary ESCC, compared with those in corresponding nontumorous esophageal epithelia (P < 0.001). Immunoreactive SnoN was detectable in 31 of 59 (52.5%) esophageal squamous cell carcinoma specimens. The levels of SnoN expression were found to correlate with the depth of invasion and recurrence (P < 0.05). Furthermore, patients with positive staining for SnoN displayed more unfavorable outcomes than patients with negative staining (P < 0.05).

Conclusion: SnoN is likely to be the target of the amplification at 3q26 in ESCC and plays an important role in the development of ESCC, influencing disease-specific survival.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / secondary
  • Chromosomes, Human, Pair 3 / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophagus / metabolism
  • Esophagus / pathology
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Immunoenzyme Techniques
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • MDS1 and EVI1 Complex Locus Protein
  • Male
  • Middle Aged
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogenes / genetics
  • RNA / genetics
  • RNA / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serpins / genetics
  • Serpins / metabolism*
  • Survival Rate
  • Telomerase / genetics
  • Telomerase / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transforming Growth Factor beta1
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • MDS1 and EVI1 Complex Locus Protein
  • MECOM protein, human
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • SKIL protein, human
  • Serpins
  • Transcription Factors
  • Transforming Growth Factor beta1
  • squamous cell carcinoma-related antigen
  • telomerase RNA
  • RNA
  • Telomerase