A gene expression profile for non‐smoking and non‐drinking patients with head and neck cancer

Abstract

Differentially expressed genes in non-smoking and non-drinking patients possibly indicate the presence of a different cellular response to carcinogenic events in these patients. Further studies are warranted to validate this gene set and explore possible therapeutic implications to improve prognosis for these patients.

The immune microenvironment of HPV-negative oral squamous cell carcinoma from never-smokers and never-drinkers patients suggests higher clinical benefit of IDO1 and PD1/PD-L1 blockade

“…In line with the increased interferon-γ activation previously observed in HNSCC from NSND [22], we observed that OSCC from NSND were strongly enriched for IFN-γ response.…”

Identification of an atypical etiological head and neck squamous carcinoma subtype featuring the CpG island methylator phenotype

“…A gene expression signature for this subtype was predictive of atypical HNSCC features in independent patient population data sets from two previous studies (Walter et al, 2013, Wichmann et al, 2015). Moreover, the CIMP-Atypical subtype displayed differential expression of genes previously reported as markers of non-smoking, non-drinking OSCCs (Farshadpour et al, 2012), that we found to be reproducibly associated with atypical HNSCC. This confirms that atypical HNSCCs display distinct gene expression patterns independent of anatomic subsite.…”

“…To further validate the CIMP-Atypical subtype, we examined a previously reported set of genes that were differentially expressed in non-smoking, non-alcohol related HNSCC relative to smoking and alcohol related HNSCC (Farshadpour et al, 2012) including 28 upregulated, and 21 downregulated genes. This study included only OSCC and oropharyngeal HNSCCs, sites primarily associated with HPV − HNSCC; therefore these gene signatures were considered putative atypical signatures: We confirmed this by validating these signatures as associated with atypical HNSCC within the TCGA, GSE65858, and GSE39366 studies (Supplementary Fig.…”

“…18 Validation of previously reported gene expression signatures associated with atypical HNSCC, in three independent patient populations. Mean expression (scaled) of genes reported as being significantly overexpressed and underexpressed in atypical HNSCC (non-smoking, non-drinking patients) relative to smoking and drinking HNSCC patients (Farshadpour et al, 2012), was higher and lower, respectively in atypical HNSCC patients in the TCGA, GSE39366 (Walter et al, 2013) and GSE65858 (Wichmann et al, 2015) studies. The number of atypical (HPV negative (HPV −) non-smokers) and smoking related HNSCC patients (HPV − smokers) are: TCGA (n = 89 atypical, 161 smoking-related), GSE39366 (n = 18 atypical, 96 smoking-related), GSE65858 (n = 23 atypical, 157 smoking-related).…”

“…The number of atypical (HPV negative (HPV −) non-smokers) and smoking related HNSCC patients (HPV − smokers) are: TCGA (n = 89 atypical, 161 smoking-related), GSE39366 (n = 18 atypical, 96 smoking-related), GSE65858 (n = 23 atypical, 157 smoking-related). Wilcoxon rank sum test p-values are indicated: *p < 0.05, ***p < 0.001.Supplementary Table 1MethylMix driver genes in the TCGA HNSCC study.Supplementary Table 2MethylMix subtypes and covariate data for TCGA HNSCC patients.Supplementary Table 3Distribution of key clinical and etiological variables between MethylMix subtypes (OSCC and LSCC separately).Supplementary Table 4Significantly mutated genes that are differentially distributed between MethylMix subtypes.Supplementary Table 5Genes upregulated and downregulated in the CIMP-Atypical subtype relative to other MethylMix subtypes.Supplementary Table 6Gene sets (GSEA) enriched in genes overexpressed in the CIMP-Atypical subtype.Supplementary Table 7Relative inferred levels of tumor infiltrating leukocyte (TAL) types in MethylMix subtypes.Supplementary Table 8Tumor suppressor and cancer mutated genes hypermethylate and/or downregulated within the CIMP-atypical subtype.Supplementary Table 9Genes stably used by the PAM classifier to classify the CIMP-Atypical subtype across all 100 folds of cross validation.Supplementary Table 10Validation of clinical attributes of the CIMP-Atypical subtype in two validation gene expression cohorts.Supplementary Table 11Levels of Farshadpour atypical HNSCC gene expression signatures (Farshadpour et al, 2012) in MethylMix subtypes (OSCC and LSCC separately).…”