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Correlation between thyroid hormone levels and the incidence and staging of bladder cancer

European Journal of Medical Research volume 30, Article number: 211 (2025) Cite this article

Abstract

Objective

Given the role of thyroid hormones (THs) in metabolism, growth and development, their involvement in carcinogenesis and cancer progression in the context of bladder cancer (BC) warrants further investigation. This study aimed to investigate the associations between TH levels and the incidence and stage of BC.

Methods

A cohort of 46 diagnosed BC patients with no history of thyroid disease, and 47 healthy controls were analysed. BC patients were classified into NMIBC and MIBC according to the 2017 TNM staging system (AJCC, 8th edition). Thyroid hormones and antibodies were measured. Statistical analysis was performed via SPSS software to evaluate differences in thyroid parameters between BC patients and healthy controls, and between non-muscle invasive bladder cancer (NMIBC) patients and muscle invasive bladder cancer (MIBC) patients.

Results

Compared with healthy controls, BC patients had higher levels of thyrotropin (TSH), total triiodothyronine (TT3), total thyroxine (TT4) and thyroglobulin and lower levels of thyroid peroxidase antibody (TPOAb). Compared with controls, both NMIBC patients and MIBC patients had elevated TT3 and TT4 levels. The proportions of NMIBC and MIBC patients were significantly greater in the high TSH, TT3, and TT4 groups than in the low TSH, TT3 and TT4 groups.

Conclusions

Elevated levels of TSH, TT3 and TT4 and low levels of TPOAb within the normal range appear to be associated with increased incidence and stage of BC. These findings suggest that TSH, TT3, TT4 and TPOAb levels may be useful for assessing BC prognosis and may provide new insights into therapeutic strategies.

Introduction

Thyroid hormones (THs) are involved in the regulation of metabolic processes, growth and development. In addition to their well-documented biological functions, thyroid hormones are involved in carcinogenesis and cancer progression. A considerable number of population-based studies have indicated a correlation between thyroid hormone levels and the incidence or progression of different types of cancer. In vivo and in vitro studies have demonstrated that triiodothyronine (T3) and thyroxine (T4) are involved in the proliferation, apoptosis, invasion and angiogenesis of cancer cells.

A two-sample Mendelian randomization study revealed a causal relationship between hypothyroidism and gastric cancer, suggesting that hypothyroidism may be associated with a reduced risk of gastric cancer [1]. Hyperthyroidism is associated with an increased risk of breast cancer, and the elevated risk of breast cancer caused by hyperthyroidism is more pronounced in postmenopausal women [2]. Orthotopically inoculated breast cancer cells exhibit accelerated growth and immune microenvironment suppression in hyperthyroid mice. In contrast, hypothyroid model mice exhibit delayed tumor growth, increased infiltration of activated CD8 + T cells, and elevated IFNγ/IL-10 ratios [3]. Liu et al. demonstrated that hypothyroidism was causally associated with a reduced likelihood of developing lung cancer, specifically lung squamous cell carcinoma, by employing a Mendelian randomization approach [4].

These studies indicate that abnormalities in thyroid function are significantly correlated with the risk and pattern of development of various types of cancer. Additionally, individual hormones have been identified as potentially influencing different types of cancer. Studies have reported that in postmenopausal women diagnosed with sigmoid colon cancer and colorectal cancer who are exposed to dietary zearalenone, as well as in males with hyperandrogenism, higher fT3/fT4 ratios are associated with poorer prognosis. Furthermore, regardless of the patient's sex, the greater the distance of the colonic tumor lesion is, the greater the fT3/fT4 ratio [5]. Studies have indicated that T3 can promote the efflux of chemotherapeutic drugs from cancer cells, thereby reducing the efficacy of chemotherapy and enabling cancer cells to evade treatment [6]. Elevated free thyroxine (FT4) levels have been shown to be associated with an increased risk of breast cancer, particularly estrogen receptor-positive tumors, highlighting its potential procarcinogenic role [7]. In a retrospective study of TH and lung cancer, researchers reported that serum thyrotrophin (TSH), TT3, and serum free triiodothyronine (FT3) levels were significantly lower, whereas serum FT4 levels were elevated in lung cancer patients compared with healthy individuals [8]. Nevertheless, the correlation between TH and cancer has been similarly demonstrated in numerous other diseases, including hepatocellular carcinoma [9], prostate cancer [10] and melanoma [11].

Bladder cancer (BC) is the tenth most common cause of cancer and the thirteenth most common cause of mortality from cancer [12]. Urothelial cancer accounts for approximately 95% of BCs [12, 13] and is categorized as non-muscle invasive bladder cancer (NMIBC) or muscle invasive bladder cancer (MIBC). NMIBC is generally associated with a favourable prognosis, although it has a high recurrence rate, with 21% of cases potentially progressing to MIBC [13]. Early and effective management of NMIBC can prevent its progression to MIBC, significantly improving long-term outcomes. The treatment of NMIBC typically involves transurethral resection and intravesical therapy. In contrast, MIBC, which has a poorer prognosis and greater risk of metastasis, often requires radical cystectomy, systemic chemotherapy, and, in some cases, radiation therapy. The optimal approach to improve the management of bladder cancer is to implement early intervention and aggressive treatment of NMIBC, with the aim of preventing its progression to MIBC. This approach has the potential to reduce mortality and improve patient quality of life [12, 13]. Nevertheless, the relationships between TH and BC or BC stages have not yet been elucidated. Consequently, it is crucial to identify biomarkers that can assist in the diagnosis of BC and to determine the stage and prognosis of BC. Consequently, the current study sought to assess the associations of bladder cancer and different cancer stages with TH levels.

Methods

Study populations

This cohort study analysed 74 diagnosed BC patients with no history of thyroid disease who were hospitalized and underwent surgical treatment at the Second Affiliated Hospital of Kunming Medical University from April 2021 to April 2022 and had undergone thyroid function tests. Twenty-eight patients with abnormal thyroid function test results at baseline were excluded, including 4 with hypothyroidism, 15 with subclinical hypothyroidism, 4 with low T3 syndrome, 3 with euthyroid Hashimoto's thyroiditis, and 2 with an unexplained decrease of in FT4. The final sample included 46 patients with BC. A total of 47 healthy controls with normal thyroid function test results were included as controls on the basis of age and sex matching. Age and sex matching is necessary because both thyroid function [14] and BC status [15, 16] vary with sex and age. The study protocol was approved by the Medical Ethics Committee of the Second Affiliated Hospital of Kunming Medical University.

Collection of clinical information

According to patient case records, BC staging was determined according to the 2017 TNM classification system (American Joint Committee on Cancer, 8th edition). All patients underwent preoperative imaging studies including abdominal and pelvic computed tomography or magnetic resonance imaging to assess tumor extent and lymph node involvement. Cryptoscopic evaluation and transurethral resection of the bladder tumor or radical cystectomy were performed, and pathological staging was confirmed by two experienced pathologists on the basis of the resected samples. For healthy controls, medical history was taken to exclude a history of thyroid disease, disease affecting thyroid function, or the use of medications that could affect thyroid function. The covariates included sex, age, thyroid function test results, blood lipids (total cholesterol [TC]; low-density lipoprotein cholesterol [LDLC]; triglycerides [TG]), liver function indicators (alanine transaminase [ALT]; aspartate transaminase [AST]), and kidney function indicators (serum creatinine [SCR]).

Laboratory analyses

Information on thyroid parameters, including thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4), free thyroxine (FT4), thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb), thyroglobulin (TG), and thyrotropin receptor antibody (TRAb) levels, was collected during the first examination after hospital admission. These parameters were measured at the SecondAffiliated Hospital of Kunming Medical University via the Abbott Architect i2000 Automatic Chemiluminescent Immunoassay Analyzer with a chemiluminescent microparticle immunoassay method. The normal ranges were 0.24–4.20 mIU/L for TSH, 0.76–2.20 µg/L for TT3, 3.39–7.14 pmol/L for FT3, 45–126 µg/L for TT4, 10.29–21.88 pmol/L for FT4, 0–115 IU/mL for TGAb, 0–34 IU/mL for TPOAb, 0–25 ng/mL for TG and 0–14 IU/L for TRAb. Overt and subclinical hypothyroidism were defined on the basis of the TSH and FT4 cut-off values. Hypothyroidism was defined as an FT4 level below the normal range and a TSH level > 4.20 mIU/L. Subclinical hypothyroidism was defined as an FT4 in the normal range and a TSH > 4.20 mIU/L. Low T3 syndrome was defined as a TSH and an FT4 within the normal range and a TT3 < 0.76 µg/L.

Statistical analysis

Statistical analyses were performed using SPSS software (version 27.0), and a p-value of < 0.05 was considered to indicate statistical significance. The Shapiro–Wilk test was used to assess the distribution characteristics of continuous data. A Student’s t-test or the Mann–Whitney U test was used to assess differences in quantitative data between the control and bladder cancer groups. The Kruskal–Wallis test and one-way ANOVA were used to evaluate differences in quantitative data among the control, MIBC, and NMIBC groups. For post hoc pairwise comparisons, the LSD method was applied for one-way ANOVA, and the Bonferroni correction was used for the Kruskal–Wallis test. Differences in the proportions of healthy controls and MIBC and NMIBC patients across different hormone-level groups were assessed using the chi-square test or Fisher’s exact test.

Results

Baseline characteristics of all patients and healthy controls included in the study

According to the inclusion and exclusion criteria, 47 healthy controls and 46 patients with bladder cancer were included in our study (Table 1). The mean age of the bladder cancer patients was 61.5 (54.75–71.25) years (median and quartiles), including 4 women and 42 men, whereas the mean age of the healthy controls was 57 (54–63) years (median and quartiles), including 3 women and 44 men. There was no significant difference between the two groups in terms of age or sex. We also evaluated the differences in blood lipids, liver function and kidney function between the two groups, and the results suggested that the BC group had higher TC (4.83 ± 0.99 vs. 4.28 ± 1.02, p = 0.012), LDLC (median and quartiles: 2.9 (2.55–3.79) vs. 2.76 (1.88–3.15), p = 0.018) and SCR (median and quartiles: 83 (76.5–93.5) vs. 75 (67–83), p = 0.019) than did the healthy control group did, whereas ALT (median and quartiles: 20 (17–24) vs. 26.00 (17–40), p = 0.045) was lower.

Table 1 The baseline characteristics of all patients and healthy controls included in the study
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Thyroid function test results

First, we assessed the differences in thyroid parameters between BC patients and healthy controls (Table 2). The results indicated that the BC group had higher TSH levels (median and quartiles: 2.59 (1.74–3.05) vs. 1.88 (1.20–2.76), p = 0.014), TT3 levels (median and quartiles: 1.10 (0.89–1.30) vs. 0.82 (0.75–1.03), p < 0.01), and TT4 levels (median and quartiles: 85.18 (78.06–98.38) vs. 67.40 (59.50–80.23), p < 0.01) and thyroglobulin levels (median and quartiles: 3.12 (1.59–4.33) vs. 2.17 (0.79–4.18), p = 0.031) than the healthy controls did, and a lower level of TPOAb (median and quartiles: 8.21 (5.48–13.34) vs. 13.42 (9.45–18.00), p < 0.01) was detected in the BC group than in the healthy controls (Fig. 1).

Table 2 Thyroid parameters of the study population
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Fig. 1
figure 1

Thyroid hormone levels are significantly different between bladder cancer patients and healthy controls. Differences in TSH (A), TT3 (B), TT4 (C), TPOAb (D) and TG (D) levels between bladder cancer patients and healthy controls. TSH thyrotropin, TT3 total-triiodothyronine, TT4 total thyroxine, TPOAb thyroid peroxidase antibodies, TG thyroglobulin

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Subgroup analysis of cancer staging

We then divided the BC patients into the NMIBC group (29) and the MIBC group (17) on the basis of the presence or absence of muscle infiltration in the pathological findings. The 20 youngest people in the control group were also excluded to avoid age differences. The differences in thyroid hormone levels among the three groups were then compared (Table 3).

Table 3 Thyroid parameters in patients with different stages of bladder cancer
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The results suggest that although the NMIBC patients were younger than the MIBC patients were (median and quartiles: 58.0 (52.0–67.0) vs. 70.0 (60.5–75.5), p = 0.004), there was no significant difference in age between the two patient groups and the healthy control group. The thyroid parameters TT3 (1.09 ± 0.24 vs. 0.87 ± 0.25, p = 0.004), FT3 (median and quartile: 4.88 (4.15–5.23) vs. 4.03 (3.57–4.63), p = 0.011) and TT4 (median and quartile: 87.00 (78.03–97.30) vs. 65.60 (58.80–80.20), p = 0.001) were higher in the NMIBC group than in the healthy control group. Moreover, TT3 (1.15 ± 0.28 vs. 0.87 ± 0.25, p = 0.001) and TT4 (median and quartiles: 83.55 (77.22–99.75) vs. 65.60 (58.80–80.20), p = 0.001) were higher in the MIBC group than in the healthy control group. Compared with healthy controls, both NMIBC patients (median and quartile: 8.30 (5.51–12.73) vs. 16.00 (10.23–20.17), p = 0.003) and MIBC patients (median and quartile: 6.91 (5.26–14.36) vs. 16.00 (10.23–20.17), p = 0.003) presented decreased TPOAb levels (Fig. 2).

Fig. 2
figure 2

Thyroid hormone levels significantly differ between patients with bladder cancer at different stages of the disease and healthy controls. Differences in TT3 (A), FT3 (B), TT4 (C) and TPOAb (D) levels between patients with different stages of bladder cancer and healthy controls. TT3 total-triiodothyronine, FT3 free triiodothyronine, TT4 total thyroxine, TPOAb thyroid peroxidase antibodies

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Subgroup analysis of hormone levels

We combined all healthy controls and BC patients and divided them into high and low hormone level groups by choosing the mean or median based on whether the hormone levels followed a normal distribution. We then assessed whether there was a difference in the populations of healthy controls and NMIBC and MIBC patients in the different hormone level groups (Table 4). The results revealed that the number of patients with NMIBC (TSH, 21 vs. 8, p < 0.01; TT3, 20 vs. 9, p = 0.005; TT4, 21 vs. 8, p < 0.01) or MIBC (TSH, 11 vs. 6, p < 0.01; TT3, 10 vs. 7, p = 0.005; TT4, 12 vs. 5, p < 0.01) was significantly greater in the high-hormone-level group than in the low-hormone-level group (Fig. 3).

Table 4 Populations in groups with different hormone levels
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Fig. 3
figure 3

Proportion of NMIBC and MIBC patients in the TSH, TT3 and TT4 groups after stratification by hormones. Different proportions of MIBC and NMIBC patients in the TSH (A), TT3 (B) and TT4 (C) groups. NMIBC non-muscle-invasive bladder cancer, MIBC muscle-invasive bladder cancer, TSH thyrotropin, TT3 total-triiodothyronine, TT4 total thyroxine

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Discussion

To our knowledge, this study is the first to investigate the correlation between TH and BC incidence and cancer stage. We found that BC patients had higher levels of TSH, TT3, TT4, TPOAb and TG than healthy controls did. Patients with NMIBC had higher levels of TT3, FT3, TT4 and TPOAb, while patients with MIBC had higher levels of TT3, TT4 and TPOAb than healthy controls did, however, these parameters were not significantly different between patients with NMIBC and those with MIBC. Additionally, the proportions of NMIBC and MIBC patients in the high TSH, TT3 and TT4 groups were significantly greater than those in the low hormone level groups.

First, many studies have suggested that elevated thyroid hormone levels may increase the risk of malignant diseases [17, 18], including solid tumors [19] and hematological malignancies [20,21,22]. A meta-analysis by Lei Z et al. suggested that compared with healthy controls, breast cancer patients exhibit a greater risk associated with elevated levels of FT3 and FT4 [23]. Higher FT4 levels are associated with a risk of prostate cancer, whereas elevated TSH levels correlate with a decreased risk [24]. Similarly, prostate cancer patients exhibit significantly higher T3 levels compared to healthy controls [25], with elevated T3 positively associated with advanced pathologic T-stages [26]. These findings may reflect crosstalk between thyroid hormones and androgen receptors [27,28,29]. However, conflicting results suggest that T3 decreases the viability, proliferation and spheroid formation potential, while increases the apoptosis of colorectal cancer stem cells [30]. Lower T3 levels are associated with significantly shorter survival in patients with gastroesophageal cancer [31]. Hypothyroidism is associated with a lower risk of rectal cancer in patients over 50 years of age [32]. Although our findings support the finding that T3 and T4 levels are higher in BC patients than in healthy individuals, we recognize that this does not establish a direct causal relationship between elevated T3 or T4 levels and BC incidence or progression. Further mechanistic studies are needed to validate this hypothesis. However, we found no difference in TH levels between NMIBC and MIBC groups, possibly because patients with MIBC are older, and thyroid hormone levels tend to be relatively low in patients of advanced age [14]. Another noteworthy finding is that although FT3 and FT4 did not have a significant effect on bladder cancer, the influence of TT4 and TT3 was still considerable. This observation highlights complexities in the current understanding that FT3 and FT4 are the primary active thyroid hormones. Our results demonstrated that bladder cancer patients had elevated levels of TG, the primary binding protein for TT3 and TT4, but the relationship between TG elevation and differences in TT3 and TT4 levels requires further study. Second, TT3 and TT4 may be indicative of the total thyroid hormone reserve within the body, whereas FT3 and FT4 represent a more transient active fraction. In chronic wasting disease, the metabolic pathways of thyroid hormones may undergo alterations (e.g., changes in deiodinase activity), resulting in the conversion of a greater proportion of TT4 to TT3 or other metabolites, while promoting the inactivation of FT4 and FT3 [26].

However, in contrast to most studies reporting that lower TSH levels increase cancer risk and progression [31, 33, 34], our results showed that BC patients had higher TSH levels than healthy controls did, with MIBC patients comprising a larger proportion of the high TSH group. While our study suggests an association between elevated TSH, TT3, and TT4 levels and bladder cancer incidence, the causal relationship remains unclear. Further investigation is needed to determine whether these thyroid hormone alterations are a cause or a consequence of BC. Possible mechanisms include stress-induced alterations in thyroid function or metabolic dysregulation related to cancer, which could affect thyroid hormone synthesis and metabolism. Further mechanistic and clinical studies with larger populations are required to clarify these hypotheses.

We also observed that BC patients had higher levels of TC and LDLC than healthy controls did, and TC and LDLC had no effect on the incidence of BC [35]. However, hypercholesterolemia is common in patients with hypothyroidism or even euthyroid patients with lower thyroxine levels [36], in contrast, BC patients have higher serum thyroxine levels. Elevated TSH levels can also impact cholesterol metabolism, leading to increased TC and LDLC levels [37]. Thus, we hypothesized that elevated TSH levels may explain increased TC and LDLC observed in BC patients.

A meta-analysis of 11 studies suggested that breast cancer patients had a higher rate of TGAb or TPOAb positivity than nonbreast disease controls did [38]. Another meta-analysis suggested that TGAb and TPOAb levels were significantly associated with breast cancer [39]. However, our results suggest that TPOAb levels are lower in patients with BC than in healthy controls and are significantly greater with increasing stages of BC. Given the role of TPOAb in immune regulation, it remains unclear whether this decrease is a contributing factor to BC progression or simply a secondary effect of immune dysregulation in cancer patients. One possible explanation is that tumor cells may suppress immune responses, including autoantibody production, to evade immune surveillance [40]. Thus, the observed decrease in TPOAb levels in BC patients may reflect an adaptive immune response. Further mechanistic studies are needed to clarify this relationship. We chose to exclude patients with autoimmune thyroiditis (AIT) for the following reasons. First, thyroid function in AIT patients is typically unstable, often presenting with periodic fluctuations in hormone levels, thyroid nodules, or other complications, which increases data heterogeneity and compromises the comparability of the research findings. Second, excluding AIT patients enables the investigation of thyroid hormone level changes in the absence of overt thyroid pathology, enhancing internal validity. Finally, autoimmune diseases inherently associated involve immune dysfunction, complicating interpretations regarding the role of thyroid hormones versus immune dysregulation in BC progression.

TH and its nuclear and cell surface receptors, as well as anti-thyroid antibodies, play important roles in the carcinogenesis and progression of many cancers, opening new avenues for research and pharmaceutical development to improve existing treatments for these patients. Our findings indicate a potential role of TH in the carcinogenesis and progression of BC, suggesting that TH levels may be considered possible biomarkers for BC prognosis.

Thyroid hormones, including triiodothyronine (T3) and thyroxine (T4), play critical roles in metabolism, growth, and development. However, their specific mechanisms in cancer initiation and progression remain incompletely understood. Studies have shown that TH regulates tumor cell functions through multiple pathways, including both genomic and non-genomic mechanisms. In the genomic pathway, T3 binds to thyroid hormone receptors (THRs) and interacts with thyroid hormone response elements (TREs) on target genes, modulating gene expression. This regulation affects tumor cell metabolism, signalling pathways, and microRNA (miRNA) networks. The role of THRs varies depending on the cancer type and disease stage. In liver cancer, THRβ1 has tumor-suppressive effects, and inhibits the PI3K/AKT signalling pathway to suppress liver cancer growth and metastasis [41, 42]. Conversely, in colorectal cancer (CRC), T3 may promote tumor progression through THRβ1 [43]. Additionally, T3-mediated overexpression of TRα1 has been linked to accelerated tumorigenesis, increased drug resistance, and increased metastatic potential [6, 44]. TH/THR signalling also influences intestinal stem cell (SC) proliferation and differentiation, with TRα1 promoting self-renewal and cell fate determination by upregulating the Wnt and Notch signalling pathways [6, 45]. Thyroid hormones also influence cancer progression by regulating miRNA expression. Several miRNAs target deiodinases and THRs, modulating TH signalling in different tissues [46]. For example, miR-21 is highly expressed in multiple cancers and promotes tumor progression by suppressing tumor suppressor genes such as PTEN and PDCD4 [47]. T3-induced upregulation of miR-21 suppresses TIAM1, thereby enhancing hepatocellular carcinoma (HCC) cell migration and invasion [48]. Given the pivotal role of miRNAs in cancer biology, small RNA therapeutics—particularly miRNA-based strategies—are emerging as promising approaches for modulating oncogenic signaling, including TH-related pathways. Recent studies have highlighted the therapeutic potential of miRNA mimics or inhibitors to restore normal gene regulation, suppress tumor progression, and enhance treatment efficacy in various cancers, including those influenced by thyroid hormone signaling [49]. Additionally, TH regulates energy metabolism through THRs, promoting oxidative phosphorylation (OXPHOS), lipid metabolism, and glucose metabolism. T3-induced metabolic reprogramming, characterized by a shift from glycolysis to OXPHOS, not only limits the tumor energy supply but also induces tumor cell differentiation, leading to the loss of undifferentiated markers [9]. In high-grade serous ovarian cancer (HGSOC), T3 has tumor-suppressive effects by promoting differentiation and oxidative metabolism. In contrast, DIO3 degrades T3 and facilitates metabolic reprogramming toward the Warburg effect, thereby driving tumor progression. Notably, DIO3 inhibition restores T3’s tumor-suppressive effects, reverses metabolic reprogramming, and suppresses tumor growth [50]. In the non-genomic pathway, T4 significantly affects on tumor growth, metastasis, and therapeutic resistance via integrin αvβ3-mediated signalling. T4 activates the MAPK/ERK1/2 and PI3K/AKT pathways, promoting tumor cell proliferation, antiapoptotic responses, and angiogenesis while enhancing resistance to chemotherapy and radiotherapy [51]. Furthermore, T4 modulates P-glycoprotein expression and DNA repair mechanisms, increasing drug efflux capacity and radioresistance in tumor cells. T4 also facilitates the expression of metastasis-associated genes, including EGFR, MMP-9, and β-catenin, through integrin αvβ3, while platelet-derived ATP release further enhances tumor cell invasion [51]. In conclusion, thyroid hormones exert complex effects on tumor initiation and progression through both genomic and non-genomic pathways, involving THRs, miRNAs, metabolic reprogramming, and integrin αvβ3-mediated signalling. These findings highlight the need for further investigation into the role of TH in cancers such as bladder cancer to identify potential therapeutic targets. Specifically, studies have shown that thyroid hormones can regulate the Wnt/β-catenin and MAPK pathways, both of which have been implicated in the development of bladder cancer. Elevated thyroid hormone levels may activate these pathways, promoting cancer cell proliferation, migration, and invasion. For example, the sustained activation of the Wnt/β-catenin pathway can continuously stimulate the proliferation, differentiation, and metastasis of bladder cancer cells and is associated with pathological grading, epithelial-mesenchymal transition (EMT), and poor prognosis in bladder cancer [52]. Additionally, activation of the MAPK signaling pathway is a key event in the progression of bladder cancer cells from non-muscle-invasive to muscle-invasive forms [53]. Further research is needed to explore how thyroid hormones interact with these pathways in bladder cancer progression.

However, the present study has certain limitations. First, the relatively small sample size reduces generalizability and may limit statistical power, increasing the risk of selection bias and weakening subgroup analyses. Expanding the sample size and conducting multicenter studies with diverse populations would improve the validity and reproducibility of these findings. Second, future research should control for additional confounders, such as BMI, smoking, and metabolic disorders, as these factors may influence thyroid hormone levels and bladder cancer risk. Smoking, metabolic abnormalities, and microbiome alterations can affect thyroid function and cancer susceptibility [12, 54, 55]. Addressing these factors would further clarify the role of thyroid hormones in bladder cancer progression. Third, due to the cross-sectional design, our study cannot establish causality between TH levels and BC incidence or staging. Prospective studies are required to validate these associations. Finally, this study primarily focused on epidemiological associations without exploring underlying mechanisms; further mechanistic research is essential.

Conclusion

To the best of our knowledge, this is the first exploratory study to investigate the correlation between thyroid hormones and bladder cancer incidence and staging. This study has potential research value and lays a preliminary foundation for future investigations on the influence of thyroid hormones on bladder cancer. Given that the initial discovery of the associations between thyroid hormones and various malignancies sparked significant discussion among scholars in related fields, we believe that the relationship between thyroid hormones and bladder cancer warrants further in-depth research.

Availability of data and materials

No datasets were generated or analysed during the current study.

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Acknowledgements

We are grateful to the participants in this study.

Funding

This study was funded by the Yunnan Provincial Department of Science and Technology (Kunming Medical University Joint Special) Science and Technology Plan Project (202301AY070001-273), Yunnan Provincial Education Department Scientific Research Fund Project (2020J0187), The Second Affiliated Hospital of Kunming Medical University Talent Echelon Cultivation Program (RCTDHB-202303), The Second Affiliated Hospital of Kunming Medical University Talent Echelon Cultivation Program (RCTDHB-202309).

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Authors and Affiliations

  1. The Second Clinical Medical College, Kunming Medical University, Kunming, China

    Jia Wang, Haihao Li & Zeping Zhou

  2. Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China

    Jia Wang, Lu Yang, Shigang Du, Yi Pan, Ling Zhao & Tingyu Ke

  3. Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China

    Haihao Li

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  1. Jia Wang
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Contributions

J.W. and H.L. contributed to the study conception and design. Data collection was performed by J.W., L.Y., S.D. and H.L.. Data analysis was performed by J.W., Y.P. and L.Z.. The first draft of the manuscript was written by J.W.. Review and editing were performed by H.L., Z.Z. and T.K. The second draft of the manuscript was revised by J.W. and H.L.. All the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.

Corresponding authors

Correspondence to Haihao Li, Zeping Zhou or Tingyu Ke.

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Ethics approval and consent to participate

All procedures performed in the study involving human participants conformed to the ethical standards of institutional and national research councils, and to the 1964 Declaration of Helsinki and its subsequent amendments or equivalent ethical standards. The study was approved by the Medical Ethics Committee of the Second Affiliated Hospital of Kunming Medical University (Ethics Approval Number: PJ-2020–156).

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The authors declare no competing interests.

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Wang, J., Yang, L., Du, S. et al. Correlation between thyroid hormone levels and the incidence and staging of bladder cancer. Eur J Med Res 30, 211 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s40001-025-02497-4

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European Journal of Medical Research

ISSN: 2047-783X

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