Next-generation sequencing identified that RET variation associates with lymph node metastasis and the immune microenvironment in thyroid papillary carcinoma

BACKGROUND: To date, although most thyroid carcinoma (THCA) achieves an excellent prognosis, some patients experience a rapid progression episode, even with differentiated THCA.

Nodal metastasis is an unfavorable predictor.

Exploring the underlying mechanism may bring a deep insight into THCA.

METHODS: A total of 108 THCA from Chinese patients with next-generation sequencing (NGS) were recruited.

It was used to explore the gene alteration spectrum of THCA and identify gene alterations related to nodal metastasis in papillary thyroid carcinoma (PTC).

The Cancer Genome Atlas THCA cohort was further studied to elucidate the relationship between specific gene alterations and tumor microenvironment.

A pathway enrichment analysis was used to explore the underlying mechanism.

RESULTS: Gene alteration was frequent in THCA.

BRAF, RET, POLE, ATM, and BRCA1 were the five most common altered genes.

RET variation was positively related to nodal metastasis in PTC.

RET variation is associated with immune cell infiltration levels, including CD8 naïve, CD4 T and CD8 T cells, etc.

Moreover, Step 3 and Step 4 of the cancer immunity cycle (CIC) were activated, whereas Step 6 was suppressed in PTC with RET variation.

A pathway enrichment analysis showed that RET variation was associated with several immune-related pathways.

CONCLUSION: RET variation is positively related to nodal metastasis in Chinese PTC, and anti-tumor immune response may play a role in nodal metastasis triggered by RET variation.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12902-024-01586-5.