Background Among thyroid malignancies, papillary thyroid carcinoma (PTC) is the most common histologic type, accounting for approximately 80%–85% of all thyroid cancers (TC). In recent years, the global incidence of PTC has been increasing, particularly among women. Although the overall prognosis of PTC is favorable, a subset of patients develop lymph node or distant metastases, which represent the primary cause of recurrence. Therefore, elucidating the factors that influence the malignant biological behavior of PTC is of great importance for developing targeted therapies, prolonging patient survival, and improving quality of life. The role of microorganisms in the progression of malignant tumors has recently garnered considerable attention. Studies have shown that Methylobacterium colonizes various solid tumors, including hepatocellular carcinoma, breast cancer, and gastric cancer, where it affects tumor proliferation, metastasis, and recurrence. However, its role in PTC remains unclear. Based on existing evidence, we hypothesized that intratumoral Methylobacterium is an important factor influencing the progression of PTC.
Objective To investigate the effect of Methylobacterium on the proliferation and migration of the PTC cell line TPC-1 and to explore the potential underlying mechanisms.
Methods Intratumoral microbiota data from patients with thyroid cancer were analyzed using the TCGA and BIC databases. Clinical samples were collected for 16S rDNA sequencing to validate differential intratumoral microbiota between early- and late-stage thyroid cancer. The effects of Methylobacterium on PTC were examined through in vitro and in vivo experiments, and the underlying mechanisms were investigated using Western blotting.
Results 1. Methylobacterium promoted the proliferation and migration of PTC cells. 2. Methylobacterium exerted these effects via its metabolite valine, which activated the PI3K/Akt/mTOR signaling pathway in a BCAT2-dependent manner.