Simultaneous high expression of PLD1 and Sp1 predicts a poor prognosis for pancreatic ductal adenocarcinoma patients

Oncotarget. 2016 Nov 29;7(48):78557-78565. doi: 10.18632/oncotarget.12447.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with few therapeutic options. Recently, insight into cancer biology suggested abnormal lipid metabolism to be a risk factor for human malignancies. As a key enzyme implicated in lipid metabolism, PLD1 was elevated in various human cancer associating with malignant phenotypes. However, little was known about its expression and function in PDAC. We showed that PLD1 was elevated in both the cell lines and clinical samples of PDAC, and it positively correlated with vascular invasion (p = 0.041) and responsible for a poor prognosis (p = 0.009). Meanwhile, we also found Sp1 to be elevated in the disease, correlating with vascular invasion (p = 0.007). Moreover, the correlation assay suggested that PLD1 positively correlated with Sp1 in the clinical sample (r = 0.390; p < 0.001) and the cell lines. Finally, we showed that co-high expression of both the factors confers the poorest prognosis for the patients, and that their simultaneous high expression might be an independent prognostic factor (p = 0.001; HR = 3.427; 95% CI 1.629-7.211).

Keywords: PDAC; PLD1; Sp1; immunohistochemistry; prognosis.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Pancreatic Ductal / genetics
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / mortality
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Phospholipase D / genetics
  • Phospholipase D / metabolism*
  • Prognosis
  • Proportional Hazards Models
  • Sp1 Transcription Factor / genetics
  • Sp1 Transcription Factor / metabolism*
  • Up-Regulation
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Sp1 Transcription Factor
  • SP1 protein, human
  • Phospholipase D
  • phospholipase D1