Relationships between SLC26A7 expressions and extra-thyroid metastasis of papillary thyroid carcinoma
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, accounting for over 80% of cases. While most PTCs grow slowly and respond well to treatment, some become aggressive—spreading beyond the thyroid (called extra-thyroid metastasis) and reducing 5-year survival rates. Until recently, scientists didn’t fully understand what drives this spread. A 2022 study from researchers at Shandong University’s Cheeloo College of Medicine and The Second Hospital of Shandong University links low activity of a gene called SLC26A7 to PTC’s metastatic potential—and points to excess iodine intake as a key trigger.
SLC26A7 is an anion transporter, a gene that helps move molecules like chloride and bicarbonate in the body. In 2019, it was discovered to also act as an iodine transporter in the thyroid—critical for producing thyroid hormones. Low SLC26A7 has already been tied to anaplastic thyroid cancer (a more aggressive form), but its role in PTC remained unstudied.
To investigate, the team first analyzed three public gene expression datasets (GSE129562, GSE60542, GSE6004) from the Gene Expression Omnibus (GEO), a database of genetic data from cancer research. They identified 190 differentially expressed genes (DEGs)—genes more or less active in tumors vs. normal thyroid tissue. From these, they focused on SLC26A7 due to its unique role in thyroid iodine transport.
Next, they used data from The Cancer Genome Atlas (TCGA), a large cancer database, to link SLC26A7 activity to patient outcomes. They found lower SLC26A7 levels correlated with shorter disease-free survival (time without recurrence) and more advanced tumor staging. Tumors also had significantly lower SLC26A7 activity than normal thyroid tissue.
To validate these findings, the team ran a hospital-based study with 35 PTC patients who had surgery at The Second Hospital of Shandong University between July 2019 and December 2019. They collected tumor tissue and adjacent normal tissue, then used real-time polymerase chain reaction (RT-PCR)—a lab technique—to measure SLC26A7 mRNA (a marker of gene activity). The study was approved by the hospital’s ethics committee and followed the Declaration of Helsinki.
The results were clear: 34.3% of tumors (12 out of 35) had low SLC26A7 activity compared to normal tissue. Patients with low SLC26A7 were far more likely to have extra-thyroid metastasis—83.3% vs. 43.5% in those with high SLC26A7. After adjusting for age, gender, and tumor size, low SLC26A7 was an independent risk factor for metastasis (odds ratio [OR] 7.1, 95% confidence interval [CI] 1.05–48.2). This means patients with low SLC26A7 were 7 times more likely to have cancer spread beyond the thyroid.
To understand why SLC26A7 is low, the team examined iodine nutrition status using urine iodine concentration (UIC)—a gold standard measure since over 90% of ingested iodine is excreted in urine. They found patients with high UIC (too much iodine) were 5 times more likely to have low SLC26A7 (50% vs. 17.6% in those with normal/low UIC). High UIC also correlated with more extra-thyroid metastasis: 77.8% of patients with high UIC had spread vs. 35.3% with normal/low UIC. After adjusting for other factors, high UIC was an independent predictor of both low SLC26A7 (OR 5.98) and extra-thyroid metastasis (OR 6.85).
The team hypothesizes that excess iodine reduces SLC26A7 activity, disrupting thyroid cell function and promoting metastasis. Previous animal studies support this: high iodine doses (7.3 mg/L) lowered iodine transporter levels in rat thyroid tissue, and low transporters are linked to more invasion and spread in thyroid cancer patients.
Like all research, this study has limitations. It is a small, cross-sectional study—so it shows a correlation, not definitive cause. Other genes or pathways may also contribute to metastasis. Larger clinical trials and animal studies are needed to confirm how SLC26A7 and iodine interact to drive spread.
Still, the findings are significant. They suggest SLC26A7 could serve as a biomarker for predicting PTC metastasis, and managing iodine intake might help reduce risk. For patients and doctors, this research adds a critical piece to the puzzle of why some PTCs become dangerous—and how to potentially prevent it.
Original study by Fengyan Huang, Juan Xiao, Lihua Wang, Yuxiang Xie, and Hongying Jia from the Department of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong University; The Second Hospital, Cheeloo College of Medicine, Shandong University; and School of Clinical Medicine, Cheeloo College of Medicine, Shandong University, published in Chinese Medical Journal (2022). doi.org/10.1097/CM9.0000000000001662
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