Copy number variation: A prognostic marker for young patients with squamous cell carcinoma of the oral tongue

Abstract

Background: The incidence of squamous cell carcinoma of the oral tongue (SCCOT) is increasing in people under age 40. There is an urgent need to identify prognostic markers that help identify young SCCOT patients with poor prognosis in order to select these for individualized treatment.

Materials and methods: To identify genetic markers that can serve as prognostic markers for young SCCOT patients, we first investigated four young (≤40 years) and five elderly patients (≥50 years) using global RNA sequencing and whole-exome sequencing. Next, we combined our data with data on SCCOT from the cancer genome atlas (TCGA), giving a total of 16 young and 104 elderly, to explore the correlations between genomic variations and clinical outcomes.

Results: In agreement with previous studies, we found that SCCOT from young and elderly patients was transcriptomically and also genomically similar with no significant differences regarding cancer driver genes, germline predisposition genes, or the burden of somatic single nucleotide variations (SNVs). However, a disparate copy number variation (CNV) was found in young patients with distinct clinical outcome. Combined with data from TCGA, we found that the overall survival was significantly better in young patients with low-CNV (n = 5) compared to high-CNV (n = 11) burden (P = 0.044).

Conclusions: Copy number variation burden is a useful single prognostic marker for SCCOT from young, but not elderly, patients. CNV burden thus holds promise to form an important contribution when selecting suitable treatment protocols for young patients with SCCOT.

Keywords: age; copy number variation; prognosis; squamous cell carcinoma of the oral tongue; whole-exome sequencing.

Figure 1

Gene expression profiles in tumor and tumor‐free tongue samples from ten patients with SCCOT. Principal component analysis (PCA) revealed distinct gene expression profiles in tumors (blue triangle) compared to tumor‐free controls (orange circle). Overall, gene expression profiles in tumors from young patients (patient ID in red) were similar to those from older patients

Figure 2

Somatic copy number variations (CNVs) analyzed by EXCAVATOR2. Circos plot showing the segmented data of 10 tumors. Each ring represents one tumor sample with corresponding patient ID. Copy number gains are marked in red, and copy number losses are marked in green. Young patients (≤40 y) (p35, p82, p98 and p111) and one patients aged 42 y (p154) are shown in the left circle. In the right circle, data from the 5 elderly patients (aged ≥ 50 y) (p119, p124, p137, p149, and p212) are shown

Figure 3

Overall survival analysis by Kaplan‐Meier method. Patients were divided into groups according to age. Overall survival analysis was performed using Kaplan‐Meier method. Log‐rank P values are shown in the plots. The red line represents patients with high‐CNV burden and the blue line patients with low‐CNV burden. According to TCGA data (TCGA‐SCCHN), there was no significant correlation between overall survival and CNV burden for the whole group of patients with SCCHN. The number of young patients (19‐40 y) with low or high CNV being 3 and 18, respectively. Combining TCGA on SCCOT with our data (ALL‐SCCOT), the overall survival rate in young patients with low‐CNV (n = 5) was significantly higher than that in young patients with high‐CNV (n = 11) (log‐rank test P = 0.044)