TIMAP 上调与 HER2-阴性乳腺癌亚型的生存呈负相关。
TIMAP Upregulation Correlates Negatively with Survival in HER2- Negative Subtypes of Breast Cancer.
机构信息
Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid, Jordan.
Department of Applied Biology, Jordan University of Science and Technology, Irbid, Jordan.
出版信息
Asian Pac J Cancer Prev. 2021 Jun 1;22(6):1899-1905. doi: 10.31557/APJCP.2021.22.6.1899.
OBJECTIVE
TIMAP expression is regulated by transforming growth factor beta 1 (TGFβ1); known for its role in breast cancer development and metastasis. Nevertheless, data on TIMAP protein expression and its association with breast cancer development are lacking. In this study, we aimed to investigate the variation in TIMAP protein expression in breast cancer tissue and its correlation with various clinicopathological characteristics of breast cancer patients and overall survival rate.
METHODS
A total of 159 paraffin-embedded tissue blocks from women diagnosed with four breast cancer subtypes (49 HER2-only, 33 Luminal A, 39 Luminal B, and 38 triple negative) were used to construct tissue microarray (TMA), followed by TIMAP immunohistochemistry (IHC). TIMAP expression was scored by two pathologists and categorized as weak (1-33% expression), moderate (34-66%), and strong (67-100%). Chi-square test and Kaplan Meier survival test were performed to determine the association between TIMAP expression and clinicopathological features and overall survival rate, respectively.
RESULTS
TIMAP protein was strongly expressed in 46 (93.9%) HER2-only, 32 (97%) luminal A, 37 (94.9%) luminal B, and 29 (76.3%) triple negative. TIMAP expression negatively associated with ER/PR expression (P=0.03), and it negatively impacted the overall survival in HER2 negative group (P=0.02).
CONCLUSION
Our findings suggest that TIMAP protein expression is upregulated in all breast cancer subtypes. However, its prognostic role is exclusively observed in HER2- negative group, suggesting a potential of targeting TIMAP in future therapeutic strategies in this group.
目的
TIMAP 的表达受转化生长因子β 1（TGFβ1）调控；其在乳腺癌的发生和转移中起作用。然而，关于 TIMAP 蛋白表达及其与乳腺癌发生的关系的数据尚缺乏。本研究旨在探讨 TIMAP 蛋白在乳腺癌组织中的表达变化及其与乳腺癌患者各种临床病理特征和总生存率的相关性。
方法
共使用 159 例来自被诊断为四种乳腺癌亚型（49 例 HER2 阳性、33 例 Luminal A、39 例 Luminal B 和 38 例三阴性）的女性的石蜡包埋组织块来构建组织微阵列（TMA），随后进行 TIMAP 免疫组织化学（IHC）检测。两位病理学家对 TIMAP 表达进行评分，并将其分为弱（表达 1-33%）、中（表达 34-66%）和强（表达 67-100%）。采用卡方检验和 Kaplan-Meier 生存分析分别确定 TIMAP 表达与临床病理特征和总生存率之间的关系。
结果
在 46 例（93.9%）HER2 阳性、32 例（97%）Luminal A、37 例（94.9%）Luminal B 和 29 例（76.3%）三阴性乳腺癌中，TIMAP 蛋白表达较强。TIMAP 表达与 ER/PR 表达呈负相关（P=0.03），且在 HER2 阴性组中对总生存率有负面影响（P=0.02）。
结论
我们的研究结果表明，TIMAP 蛋白在所有乳腺癌亚型中均呈上调表达。然而，其预后作用仅在 HER2 阴性组中观察到，提示 TIMAP 可能成为该组未来治疗策略的潜在靶点。
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