Gene expression patterns through oral squamous cell carcinoma development: PD-L1 expression in primary tumor and circulating tumor cells

Oncotarget. 2015 Aug 28;6(25):20902-20. doi: 10.18632/oncotarget.3939.

Abstract

Oral squamous cell carcinoma (OSCC) is the most common tumor of the oral cavity and has been associated with poor prognosis. Scarce prognostic markers are available for guiding treatment and/or sub-classifying patients. This study aims to identify biomarkers by searching for genes whose expression is increased or decreased during tumor progression (through T1 to T4 stages). Thirty-six samples from all tumor size stages (from T1 to T4) were analyzed using cDNA microarrays. Selected targets were analyzed by immunohistochemistry and in circulating tumor cells by immunofluorescence and Nanostring. Correlation was shown between PD-L1 and tumor size and lymph node metastasis, HOXB9 and tumor size, BLNK and perineural invasion, and between ZNF813 and perineural invasion. PD-L1 positivity was an independent prognostic factor in this cohort (p = 0.044, HH = 0.426). In CTCs from patients with locally advanced OSCC, we found a strong cytoplasmatic expression of PD-L1. PD-L1 is a ligand of PD-1 and is believed to limit T cell activity in inflammatory responses and limit autoimmune diseases. We demonstrated an important role for PD-L1 in primary tumors according to tumor size, and in disease specific survival. Therefore, we could further determine individuals with PD-L1+ CTCs, and possibly follow treatment using CTCs.

Keywords: PD-L1; Pathology Section; circulating tumor cells; gene expression; oral squamous cell carcinoma; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Autoimmune Diseases / metabolism
  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Cohort Studies
  • Cytoplasm / metabolism
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Homeodomain Proteins / metabolism
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mouth Neoplasms / blood
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / mortality
  • Neoplastic Cells, Circulating / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Proportional Hazards Models
  • Tissue Banks
  • Treatment Outcome

Substances

  • Adaptor Proteins, Signal Transducing
  • B cell linker protein
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • DNA-Binding Proteins
  • HOXB9 protein, human
  • Homeodomain Proteins
  • ZNF813 protein, human