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TIMP3 基因表达对甲状腺癌的长期影响:治愈模型分析。

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

机构信息

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

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

出版信息

Asian Pac J Cancer Prev. 2024 Oct 1;25(10):3627-3634. doi: 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.

摘要

背景

甲状腺癌是最常见的内分泌恶性肿瘤。TIMP3 是一种金属蛋白酶抑制剂,可抑制甲状腺癌细胞的血管生成、侵袭和转移。本研究旨在探讨 TIMP3 基因表达及其它相关因素对甲状腺癌患者生存率和治愈率的长期影响。

方法

本研究为历史队列研究,基于 TCGA 数据库,收集了 507 例甲状腺癌患者和 59 例对照样本的临床信息。采用 Kaplan-Meier 曲线和对数秩检验进行组间比较。应用威布尔混合和非混合治愈模型探讨 TIMP3 基因表达与生存时间及治愈状态的关系。所有统计分析均采用 R 语言进行。

结果

本研究共纳入 507 例甲状腺癌患者和 59 例正常组织对照者,患者平均年龄为 47.93±15.96 岁,正常组织对照者为 47.06 ± 17.74 岁。患者中男性占 26.8%,高表达占 69.6%,研究期间死亡 3.16%。与正常组织对照者相比,肿瘤阳性患者 TIMP3 表达明显降低(p<0.001)。Kaplan-Meier 曲线显示,经过 2000 天的随访,78%的患者治愈。结果表明威布尔混合治愈模型优于非混合治愈模型。而且,校正其它因素后,TIMP3 高表达与患者长期恢复机会增加相关。具体而言,TIMP3 高表达患者的治愈可能性约为其它患者的 2.3 倍。

结论

TIMP3 表达对甲状腺癌患者的治愈率具有保护作用,尽管它似乎不会影响短期生存。本研究提示靶向 TIMP3 可能为甲状腺癌提供新的治疗靶点,并可能成为甲状腺癌预后的潜在生物标志物。

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