The incidence of thyroid cancer is steadily increasing, with PTC being the most prevalent subtype. However, current laboratory tests lack a reliable indicator for PTC screening. GAL-3 is commonly employed in the pathological diagnosis of thyroid cancer. Consequently, we investigated the feasibility of preoperatively distinguishing between benign and malignant thyroid nodules through the detection of the serum biomarker GAL-3. The results suggest that serum GAL-3 detection holds promise for differentiating between benign and malignant thyroid diseases. Additionally, the combined detection of GAL-3 with HER2 and Ki-67 can significantly enhance the diagnostic efficacy of thyroid diseases.
In the assessment of thyroid function markers, including TT3, TT4, FT3, FT4, TSH, TPO-Ab, and PTH, no significant differences were observed between the PTC and benign thyroid disease groups. However, there was a notable elevation in thyroglobulin levels in the benign disease group compared to the PTC group. While, elevated serum thyroglobulin levels across various thyroid disorders contribute to the consideration by both the European and American Thyroid Associations that preoperative thyroglobulin testing is insensitive and non-specific for thyroid cancer [15, 16]. Similarly, the 2017 Chinese Expert Consensus on the Clinical Application of Serum Markers in Thyroid Cancer does not recommend using thyroglobulin to differentiate between benign and malignant thyroid tumors [17]. Aligned with the conclusions of Rok P’s study, our findings also reveal a significant elevation in serum TG-Ab levels in PTC patients compared to those with benign thyroid diseases [18].
In this study, we preliminarily established a reference range for serum GAL-3 in a normal healthy population, which ranged from 3.0 to 14.3 ng/ml. This range is lower than the serum GAL-3 levels reported in Sonia L's 2013 study, where the 97.5th percentile was noted as 17.9 ng/ml. Consistently, we observed higher serum GAL-3 levels in males compared to females, although there was no significant difference between the two groups [19].
In recent years, there has been a growing body of research on the correlation between serum GAL-3 and PTC. Corresponding to our study findings, Li 2021 [20] proposed that a combined assessment of serum long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) and GAL-3 could serve for the discrimination of benign and malignant thyroid diseases. In Li 2021, the area under the serum GAL-3 curve was 0.817, surpassing our curve's area. However, it is worth noting that the control group in Li 2021 predominantly comprised patients with thyroid adenomas, while ours mainly featured individuals with nodular thyroid goiters. Similarly, Makki FM 2013 [21] discovered no significant difference in serum CK19 levels between PTC and benign thyroid tumor patients. Nonetheless, the study suggests that further exploration is warranted to investigate potential disparities in serum GAL-3 levels between benign and malignant thyroid diseases.
In contrast to another study, Yu 2020 [22], which suggests a significant difference in serum GAL-3 levels between PTC patients with lymph node metastasis and those without, our research results indicate no significant difference between these two groups. The different findings may be explained by the inclusion of a limited sample size with 27 cases in the lymph node metastasis group and 23 cases in the non-metastasis group in Yu 2020. Compared with Li 2021 which also demonstrated a significant difference in serum GAL-3 levels between PTC patients with and without lymph node metastasis, our study primarily included patients with smaller tumors (≤ 1cm) and those without lymph node metastasis, where Li 2021 included PTC patients with larger tumor ((≥ 2cm) and those with lymph node metastasis.
One of the limitations of our study is that the control group primarily consisted of patients with benign thyroid diseases who required surgery for thyroid nodules. These nodules were typically larger, often exceeding 3cm, and in some cases, presented with features such as bleeding and calcification. Therefore, we plan to select patients with thyroid nodules smaller than 3cm to investigate whether there are differences in serum GAL-3 levels between PTC and patients with benign thyroid nodules in the future. Additionally, we aim to explore the association between serum GAL-3 levels in patients with PTC and tumor size as well as lymph node metastasis. Specifically, our focus will be on patients with a tumor diameter of ≥ 2cm and those with lymph node metastasis in the next phase of our research.