Downregulation of TAP1 in Tumor-Free Tongue Contralateral to Squamous Cell Carcinoma of the Oral Tongue, an Indicator of Better Survival

Abstract

Oral cancers are surrounded by epithelium that histologically might seem normal, but genetically has aberrations. In patients with squamous cell carcinoma of the oral tongue (SCCOT), it is therefore important to study not only the tumor but also the clinically tumor-free contralateral tongue tissue that remains in the patient after treatment to map changes of prognostic and/or diagnostic value. The transporter associated with antigen processing (TAP) dimer is a key factor in the process of activating cytotoxic T cells. By downregulating the expression of TAP, tumor cells can escape cytotoxic T cell recognition. Biopsies from tumor and clinically tumor-free contralateral tongue tissue in 21 patients with SCCOT were analyzed together with tongue biopsies from 14 healthy individuals, which served as the control group. Dividing patients into TAP1-high and TAP1-low groups according to the median TAP1 level in tumor-free samples showed that patients with lower TAP1 mRNA levels in tumor-free samples had better overall (p = 0.003) and disease-free survival (p = 0.002). The results showing that TAP1 levels in tumor-free tongue tissue contralateral to the SCCOT correlate with survival is an important contribution to early diagnosis and follow up of SCCOT.

Keywords: MHC I; SCCOT; TAP1; field cancerization.

Figure 1

Microarray results of (A) TAP1 and (B) TAP2 mRNA levels in tongue from healthy volunteers, tumor-free samples and SCCOT samples. (C) Correlation between TAP1 and TAP2 levels (p < 0.001). (D) Real-time quantitative PCR (RT-qPCR) confirmation of microarray data for TAP1 (spearman correlation coefficient: 0.841, p < 0.001).

Figure 2

The influence of TAP1 levels in tumor-free samples on patient survival. Kaplan–Meier curves of overall (A) and disease-free (B) survival. Blue lines represent patients with low TAP1 levels, and red lines patients with high TAP1 levels. Log-rank test for overall (p = 0.003) and disease-free survival (p = 0.002). N = number of samples.

Figure 3

TCGA-HNSC (The Cancer Genome Atlas-head and neck squamous cell carcinoma) cohort data. Plots show TAP1 levels in tumors and tumor-free samples, the latter denominated “normal” in TCGA, for (A) the whole group of squamous cell carcinoma of the head and neck–SCCHN (p < 0.001) and (B) for squamous cell carcinoma of the tongue (SCCOT) only (p < 0.001).

Figure 4

The influence of TAP1 levels in tumor-free samples from the TCGA-HNSC cohort on patient survival. Kaplan–Meier curves of overall survival for (A) tumor-free samples (denominated “normal” by TCGA), (B) matched tumor samples, and (C) all SCCHN tumors available in the TCGA database. Blue lines represent patients with low TAP1 levels, and red lines indicate patients with high TAP1 levels. N = number of samples