Long-Term Effect of TIMP3 Gene Expression on Thyroid Cancer: A Cure Model Analysis

Dindarloo, Mohammad Mehdi; Fendereski, Afsaneh; Kashi, Zahra; Yazdani -Charati, Jamshid

doi:10.31557/APJCP.2024.25.10.3627

Long-Term Effect of TIMP3 Gene Expression on Thyroid Cancer: A Cure Model Analysis

Document Type : Research Articles

Authors

¹ Department of Epidemiology and Biostatistics, School of Health, Mazandaran University of Medical Sciences, Sari, Iran.

² Diabetes Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

10.31557/APJCP.2024.25.10.3627

Abstract

Background: Thyroid cancer is the most common endocrine malignancy. TIMP3, a metalloproteinase inhibitor, can inhibit angiogenesis, invasion, and metastasis in thyroid cancer. In this study, we investigated the long-term effect of TIMP3 gene expression and other associated factors on the survival rate and cure probability of thyroid cancer patients. Methods: In this historical cohort study, clinical information was collected from 507 thyroid cancer patients and 59 control samples based on the TCGA database. The Kaplan-Meier curve and log-rank test were employed for group comparisons. Weibull mixture and non-mixture cure models were utilized to explore the association between TIMP3 gene expression and survival time, as well as cure status. All statistical analyses were conducted using the R language. Results: There were 507 thyroid cancer patients and 59 normal tissue participants in the study with an average age of 47.93±15.96 and 47.06 ± 17.74 years respectively. A total of 26.8 percent of patients were male, 69.6 percent had high expression, and 3.16 percent died during the study. Compared with normal tissue participants, tumor-positive patients had significantly lower TIMP3 expression (p<0.001). After 2,000 days of follow-up, 78 percent of patients were cured based on Kaplan-Meier curves. The results show that the Weibull mixture cure model is superior to the non-mixture cure model. Moreover, after controlling for other factors, higher TIMP3 expression was associated with an increased chance of long-term recovery in patients. Specifically, the odds of cure in patients with higher TIMP3 expression were approximately 2.3 times greater than others. Conclusions: TIMP3 expression has a protective effect on cure probability in thyroid cancer patients, even though it does not appear to affect short-term survival. This study suggests that targeting TIMP3 may offer promise for thyroid cancer and may be a potential biomarker for thyroid cancer prognosis.

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