Levels of dipeptidyl peptidase 4 (DPP4) are higher in medullary thyroid carcinoma (MTC) tissues than in paracancerous tissues, a new study published in the International Journal of Endocrinology found.

DPP4 levels could potentially be used as a prognostic marker of thyroid carcinomas, and DPP4 may be an effective target for immunotherapy, according to the authors of the study.

Many types of cancer express DPP4. However, the relationship between the enzyme and thyroid carcinoma is not well known.

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To assess the expression levels of DPP4 in thyroid carcinomas and explore the potential link between these levels and disease prognosis, a team of researchers from the Cheeloo College of Medicine at Shandong University in Qingdao, China, systematically analyzed data from the Cancer Genome Atlas, Genotype-Tissue Expression, and Gene Expression Omnibus databases. 

Read more about the treatment of MTC

The team then collected 18 pairs of fresh thyroid carcinoma tissues and adjacent paracancerous tissues. They measured the levels of DPP4 messenger RNA (mRNA) using real-time quantitative polymerase chain reaction (PCR). They then immunohistochemically analyzed 12 pairs of MTC and paracancerous tissues to measure the levels of DPP4 protein.

Bioinformatics analysis showed that the levels of DPP4 mRNA were significantly higher in thyroid carcinomas than in paracancerous tissues, with the highest expression seen in MTC.

When they compared samples obtained from patients with different clinical characteristics, the researchers saw that the levels of DPP4 expression were also different. Accordingly, disease-free survival was lowest when the DPP4 levels were highest. Moreover, DPP4 levels significantly correlated with immune cell infiltration and immune response. They were also positively associated with 21 immune checkpoint genes. 

The PCR results revealed that the relative mRNA expression levels of DPP4 were significantly upregulated in the 18 thyroid carcinoma tissues compared to those of the paracancerous tissues, and the immunohistochemistry results showed that levels of DPP4 protein were significantly higher in the 12 MTC samples than in the paracancerous tissues.

“DPP4 may be a carcinogenic gene of [thyroid carcinoma], which is related to the prognosis and antitumor immunity of [thyroid carcinoma] patients,” the authors concluded. 


Gao X, Le Y, Geng C, Jiang Z, Zhao G, Zhang P. DPP4 is a potential prognostic marker of thyroid carcinoma and a target for immunotherapy. Int J Endocrinol. 2022;2022:5181386. doi:10.1155/2022/5181386