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. 2023 Aug;9(4):711-720.
doi: 10.1002/cre2.739. Epub 2023 Jun 5.

Identification of novel oncogenes in oral cancer among elderly nonsmokers

Hitoshi Inoue  1 , Masataka Hirasaki  2 , Yasunao Kogashiwa  1 , Yutaka Nakachi  3 , Kiyomi Kuba  1 , Yasuhiro Ebihara  1 , Mitsuhiko Nakahira  1 , Masanori Yasuda  4 , Akihiko Okuda  5 , Masashi Sugasawa  1
Affiliations

Identification of novel oncogenes in oral cancer among elderly nonsmokers

Hitoshi Inoue et al. Clin Exp Dent Res. 2023 Aug.

Abstract

Objectives: In recent years, an increase in oral cancer among elderly nonsmokers has been noted. The aim of this study was to identify novel oncogenes in oral cancer in older nonsmokers.

Material and methods: Whole-exome sequencing (WES) data from 324 oral cancer patients were obtained from The Cancer Genome Atlas. Single nucleotide variants (SNVs) and insertions/deletions (INDELs) were extracted from the WES data of older patients. Fisher's exact test was performed to determine the specificity of variants in these genes. Finally, SNVs and INDELs were identified by target enrichment sequencing.

Results: Gene ontology analysis of 112 genes with significant SNVs or INDELs in nonsmokers revealed that nonsynonymous SNVs in HECTD4 were significantly more frequent in nonsmokers than in smokers by target enrichment sequencing (p = .02).

Conclusions: Further investigation of the function of HECTD4 variants as oncogenes in older nonsmokers is warranted.

Keywords: HECTD4; elderly; nonsmokers; oral cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
As a result of the analysis of the TCGA data, those aged 65 years and older were defined as elderly, and classified into smoking and nonsmoking groups by gender. (a) The number of male and female components of the 328 anonymized primary oral cancer patients identified in the TCGA database. (b) The smoking trends of primary oral cancer patients aged 65 years and older identified in the TCGA database were shown. (c) Four groups were created according to age and smoking propensity, and the gender ratio of each group was shown. TCGA, The Cancer Genome Atlas.
Figure 2
Figure 2
Results of GO analysis of 112 genes with significant SNVs in the nonsmoker group. (a) SNVs or INDELs were detected in 6956 genes in nonsmoker and 9511 genes in smokers. The commonality of each gene was represented by a Venn diagram. (b) Genes with SNVs or INDELs were tested for specificity in smoking tendency using Fisher's exact test. (c) The results of GO analysis of the genes for which SNVs or INDELs were found specifically in nonsmokers are shown. GO, gene ontology; INDEL, insertion/deletion; SNV, single nucleotide variant.
Figure 3
Figure 3
Result of original target enrichment sequencing in our elderly clinical cases. (a) The trend of the mean depth for each of the 63 multiplexed samples is shown in the violin plot. (b) The trend of the coverage ratio for each of the 63 multiplexed samples is shown in the violin plot. (c, d) The number of SNVs or INDELs identified by original target enrichment sequencing is shown. Classification was performed for each of the six regions (c). Classification was performed by variant type (d). INDELs, insertions/deletions; SNV, single nucleotide variant.
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