347 Genes Associated with Prognosis in Thyroid Cancer

LARS composite.jpg
Immunohistochemical staining of LARS shows high (left) and low (right) expression in thyroid cancer samples.
VAMP8 composite.jpg
Immunohistochemical staining of VAMP8 shows high (left) and low (right) expression in thyroid cancer samples.

Although thyroid cancer is fairly common, it has a relatively good prognosis compared to other cancers. Survival varies depending on type of thyroid cancer, with papillary carcinoma, the most common type, having the highest survival rate. By using a systems level approach to analyze the thyroid cancer proteome based on clinical metadata and genome-wide transcriptomics data, 374 genes were found to be associated with prognostic outcome.

Each year, 0.5-10 per 100,000 people are diagnosed with thyroid cancer, 2-4 times more frequently in women compared to men for reason yet unknown. Family history and hereditary conditions have been identified as risk factors, however, most patients do not have any of them. The most common form of thyroid cancer is papillary carcinoma (70-80%), followed by follicular carcinoma (10-20%), medullary carcinoma (5-10%) and anaplastic carcinoma (2-10%). Classification based on histological features and tumor aggressiveness are crucial for correct treatment. For tumors with unusual histology, immunohistochemistry is an important diagnostic tool in addition to the commonly used microscopical examination. Prognosis in general is good, with a 10-year relative survival rate for most papillary carcinomas. Apart from age, where young patients have a considerably better prognosis, the size of the primary tumor and the tumor stage are the most important prognostic factors.

The analysis of prognostic genes in thyroid cancer was based on publicly available gene expression data and clinical metadata from the Cancer Genome Atlas (TCGA), consisting of 291 patients. According to the analysis, 374 genes were associated with prognostic outcome, out of which 186 genes were associated with unfavourable prognosis and 161 genes with favourable prognosis.

Leucyl-tRNA synthetase, LARS, is shown to be associated with unfavourable prognosis in patients with thyroid cancer. It encodes an amino acid binding protein involved in regulation of protein synthesis. Immunohistochemical staining of LARS shows varying cytoplasmic expression in thyroid cancer samples (Figure 1).

A gene associated with favourable prognosis is VAMP8, vesicle associated membrane protein 8. The encoded protein is a member of the SNARE protein family, known to be essential for membrane fusion. In particular, this protein plays a key role in autophagy by controlling the fusion of autophagosome membrane with lysosome membrane. Immunohistochemical staining of VAMP8 shows differential cytoplasmic expression in thyroid cancer samples (Figure 2).

Explore the Thyroid Cancer Proteome and search for your gene of interest in our Pathology Atlas!

References and links

Uhlén M et al, 2017. A pathology atlas of the human cancer transcriptome. Science. PubMed: 28818916

DOI 10.1126/science.aan2507

Histology dictionary - Thyroid cancer

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