The head and neck cancer proteome


Head and neck cancer arises in the nasal cavity, sinuses, lips, mouth, salivary glands, throat, or larynx (voice box). Head and neck cancers are common in several regions of the world where tobacco usage and alcohol consumption is high. Head and neck cancers comprise approximately 10% of all newly diagnosed cancers in the western world, but one-third in India. The variation in incidence between regions is mostly related to the relative distribution of major risk factors such as tobacco and alcohol consumption. Head and neck cancer has a 5-year survival rate of approximately 60%, depending on locations on primary tumor and grade.

There is increasing evidence that viruses might contribute to the cause of head and neck cancer. DNA from human papilloma virus (HPV) has been detected in cancerous tissue from head and neck and infection with Epstein-Barr virus is associated with nasopharyngeal cancer. Surprisingly, patients with advanced forms of cancer in the upper portion of the throat have better outcome if the tumor is positive for HPV. Occurrence of head and neck cancer in young adults and in non-users of tobacco and alcohol suggests that genetic predisposition may be a possible etiological factor.

Most head and neck cancers arise from squamous epithelium and are squamous cell carcinomas of different histologic grades. The tumor cells in well-differentiated cancers closely resemble normal squamous epithelium, whereas poorly differentiated cancers are difficult to classify as being of squamous epithelial origin. Salivary gland tumors (mainly adenocarcinomas) comprise a minority of head and neck tumors.

Here, we explore the head and neck cancer proteome using TCGA transcriptomics data and antibody based protein data. 792 genes are suggested as prognostic based on transcriptomics data from 499 patients; 341 genes associated with unfavourable prognosis and 451 genes associated with favourable prognosis.

TCGA data analysis


In this metadata study we used data from TCGA where transcriptomics data was available from 499 patients with head and neck cancer. The total dataset included 133 females and 366 males. Around 56% of the patients (281 patients) were still alive at the time of data collection. The stage distribution was stage i) 25 patients, stage ii) 69 patients, stage iii) 78 patients, stage iv) 259 patients and 68 patients with missing stage information.

Unfavourable prognostic genes in head and neck cancer


For unfavourable genes, higher relative expression levels at diagnosis gives significantly lower overall survival for the patients. There are 341 genes associated with unfavourable prognosis in head and neck cancer. In Table 1, the top 20 most significant genes related to unfavourable prognosis are listed.

LIMA1 is a gene associated with unfavourable prognosis in head and neck cancer. The best separation is achieved by an expression cutoff at 38.2 fpkm which divides the patients into two groups with 36% 5-year survival for patients with high expression versus 54% for patients with low expression, p-value: 1.76e-6. Immunohistochemical staining using an antibody targeting LIMA1 (HPA052645) shows differential expression pattern in head and neck cancer samples.

LIMA1 - survival analysis p<0.001
LIMA1 - high expression
LIMA1 - low expression

Table 1. The 20 genes with highest significance associated with unfavourable prognosis in head and neck cancer.

Gene Description Predicted localization mRNA (cancer) p-value
DKK1 dickkopf WNT signaling pathway inhibitor 1 Secreted 8.6 4.35e-8
CAMK2N1 calcium/calmodulin dependent protein kinase II inhibitor 1 Intracellular 9.5 1.37e-7
NDFIP1 Nedd4 family interacting protein 1 Membrane 13.5 2.33e-7
AIG1 androgen induced 1 Membrane,Secreted 5.3 3.25e-7
SEC61G Sec61 translocon gamma subunit Membrane 56.4 4.64e-7
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Favourable prognostic genes in head and neck cancer


For favourable genes, higher relative expression levels at diagnosis gives significantly higher overall survival for the patients. There are 451 genes associated with favourable prognosis in head and neck cancer. In Table 2, the top 20 most significant genes related to favourable prognosis are listed.

CALML5 is a gene associated with favourable prognosis in head and neck cancer. The best separation is achieved by an expression cutoff at 60.6 fpkm which divides the patients into two groups with 52% 5-year survival for patients with high expression versus 37% for patients with low expression, p-value: 2.59e-5. Immunohistochemical staining using an antibody targeting CALML5 (HPA040725) shows differential expression pattern in head and neck cancer samples.

CALML5 - survival analysis p<0.001
CALML5 - high expression
CALML5 - low expression

Table 2. The 20 genes with highest significance associated with favourable prognosis in head and neck cancer.

Gene Description Predicted localization mRNA (cancer) p-value
ZNF846 zinc finger protein 846 Intracellular 1.2 5.25e-8
SZT2 seizure threshold 2 homolog (mouse) Intracellular 2.1 1.47e-7
GZMM granzyme M Intracellular,Secreted 1.7 1.87e-7
FGD3 FYVE, RhoGEF and PH domain containing 3 Intracellular 2.2 2.23e-7
PPFIA3 PTPRF interacting protein alpha 3 Intracellular 3.9 6.46e-7
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The head and neck cancer transcriptome


The transcriptome analysis shows that 69% (n=13428) of all human genes (n=19479) are expressed in head and neck cancer. All genes were classified according to the head and neck cancer-specific expression into one of five different categories, based on the ratio between mRNA levels in head and neck cancer compared to the mRNA levels in the other 16 analyzed cancer tissues. 263 genes show some level of elevated expression in head and neck cancer compared to other cancers (Figure 1). The elevated category is further subdivided into three categories as shown in Table 3.

Figure 1. The distribution of all genes across the five categories based on transcript abundance in head and neck cancer as well as in all other cancer tissues.

Table 3. Number of genes in the subdivided categories of elevated expression in head and neck cancer.

Category Number of genes Description
Tissue enriched 21 At least five-fold higher mRNA levels in a particular cancer as compared to all other cancers
Group enriched 117 At least five-fold higher mRNA levels in a group of 2-7 cancers
Tissue enhanced 125 At least five-fold higher mRNA levels in a particular cancer as compared to average levels in all cancers
Total 263 Total number of elevated genes in head and neck cancer

Additional information


Head and neck cancers are classified using the TNM System. It describes the extent of the primary tumor (T stage), the absence or presence of spread to nearby lymph nodes (N stage) and the absence or presence of distant spread, or metastasis (M stage). Once the T, N and M are determined, a stage of I, II, III or IV is assigned. Stage I cancers are small, localized and usually curable, while stage II and III cancers typically are locally advanced and/or have spread to local lymph nodes. Stage IV cancers are usually metastatic (have spread to distant parts of the body) and are generally considered inoperable. Early stage (Stage I and II) cancers yield a 60-95% cure rate, that falls to 25% for Stage IV tumors.

Relevant links and publications


Uhlen M et al, 2017. A pathology atlas of the human cancer transcriptome. Science.
PubMed: 28818916 DOI: 10.1126/science.aan2507

Cancer Genome Atlas Research Network et al, 2013. The Cancer Genome Atlas Pan-Cancer analysis project. Nat Genet.
PubMed: 24071849 DOI: 10.1038/ng.2764

UhlĂ©n M et al, 2015. Tissue-based map of the human proteome. Science
PubMed: 25613900 DOI: 10.1126/science.1260419

Histology dictionary - Head and neck cancer