基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The expression of epidermal growth factor receptor 2 and its relationship with tumor-infiltrating lymphocytes and clinical pathological features in breast cancer patients.
The expression of epidermal growth factor receptor 2 and its relationship with tumor-infiltrating lymphocytes and clinical pathological features in breast cancer patients.
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乳腺癌(BC)是女性常见的恶性肿瘤,其发生和发展受多种因素影响。本研究旨在探讨人表皮生长因子受体-2(HER-2)在BC中的表达及其与TIL(肿瘤浸润淋巴细胞)(TILs)和BC患者临床病理特征的关系。收集470例BC患者的数据,并评估TIL水平。采用免疫组化(IHC)进一步分析TILs与临床病理参数的关系,以及CD8和HER-2的表达。免疫组化结果显示,HER-2阳性表达率为28.72%(135/470),其表达强度随组织学分级升高而显著增加(低级别:15.2%,中级别:28.5%,高级别:42.6%,P < 0.05)。CD8阳性细胞主要位于肿瘤间质中,阳性率为56.38%(265/470)。
此外,高TIL水平组的阳性表达强度显著高于低TIL水平组(高TIL组:78.9%,低TIL组:35.4%,P < 0.05)。统计结果表明,37.45%(176/470)的病例表现为无或低TIL水平,42.34%(199/470)表现为中等TIL水平,20.21%(95/470)表现为高TIL水平。TIL水平与BC组织学分级显著相关(高TIL组中高级别病例百分比:65.3%,低TIL组:22.1%,P < 0.05)、Ki-67指数(高TIL组:45.2% 12.3%,低TIL组:25.6% 10.8%,P < 0.05)、脉管癌栓(VTE)(高TIL组VTE阳性率:38.9%,低TIL组:12.4%,P < 0.05)、淋巴结转移(LNM)(高 TIL 组 LNM 阳性率:52.6%,低 TIL 组:28.4%,P < 0.05)以及雌激素受体(ER)表达(高 TIL 组 ER 阴性率:68.4%,低 TIL 组:32.1%,P < 0.05)。
Spearman 相关性分析显示,TILs 与 HER-2(r = 0.149,P = 0.002)以及 CD8(r = 0.593,P = 0.001)呈正相关。GEPIA 数据库分析显示,HER-2 高表达患者的无病生存期(DFS)显著低于低表达患者(风险比 [HR] = 1.45,P = 0.003),而 CD8 高表达患者的 DFS 显著高于低表达患者(HR = 0.72,P = 0.001)。在 HER-2 阳性 BC 患者中,TIL 水平与 HER-2 和 CD8 表达呈正相关(HER-2 高表达组:TIL 高表达率 48.6%,HER-2 低表达组:TIL 高表达率 15.2%,P < 0.05)。HER-2 阳性 BC 患者中 TIL 水平与 HER-2 和 CD8 表达均呈正相关。TIL 水平与 BC 患者预后密切相关,这可能为 BC 的精准治疗提供理论依据。
Breast cancer (BC) is a common malignant tumor with a frequent occurrence in women, and its occurrence and progression are influenced by various factors. This work aimed to investigate the expression of human epidermal growth factor receptor-2 (HER-2) in BC and its relationship with tumor-infiltrating lymphocytes (TILs) and the clinical pathological features of BC patients. Data from 470 BC patients were collected, and TIL levels were assessed.
Immunohistochemistry (IHC) was performed to further analyze the relationship between TILs and clinical pathological parameters, as well as the expression of CD8 and HER-2. Immunohistochemical results revealed that the HER-2-positive expression rate was 28. 72% (135/470), and its expression intensity significantly increased with higher histological grades (low grade: 15. 2%, moderate grade: 28. 5%, high grade: 42. 6%, P < 0. 05). CD8-positive cells were predominantly located in the tumor stroma, with a positive rate of 56. 38% (265/470).
Moreover, the positive expression intensity in the high TIL level group was significantly higher than in the low TIL level group (high TIL group: 78. 9%, low TIL group: 35. 4%, P < 0. 05). The statistical results indicated that 37. 45% (176/470) of cases exhibited no or low TIL levels, 42. 34% (199/470) showed moderate TIL levels, and 20. 21% (95/470) presented high TIL levels. TIL levels were significantly associated with histological grade of BC (percentage of high-grade cases in the high TIL group: 65. 3%, in the low TIL group: 22. 1%, P < 0. 05), Ki-67 index (high TIL group: 45. 2% 12. 3%, low TIL group: 25. 6% 10. 8%, P < 0. 05), vascular tumor embolism (VTE) (VTE-positive rate in the high TIL group: 38. 9%, in the low TIL group: 12. 4%, P < 0. 05), lymph node metastasis (LNM) (LNM-positive rate in the high TIL group: 52. 6%, in the low TIL group: 28. 4%, P < 0. 05), and estrogen receptor (ER) expression (ER-negative rate in the high TIL group: 68. 4%, in the low TIL group: 32.
1%, P < 0. 05). Spearman correlation analysis revealed a positive correlation between TILs and HER-2 ( r = 0. 149, P = 0. 002), as well as CD8 ( r = 0. 593, P = 0. 001). Analysis of the GEPIA database showed that patients with high HER-2 expression had significantly lower disease-free survival (DFS) compared to those with low expression (hazard ratio [HR] = 1. 45, P = 0. 003), while patients with high CD8 expression exhibited significantly higher DFS than those with low expression (HR = 0.
72, P = 0. 001). In HER-2-positive BC patients, TIL levels were positively correlated with HER-2 and CD8 expression (high HER-2 expression group: TIL high expression rate 48. 6%, low HER-2 expression group: TIL high expression rate 15. 2%, P < 0. 05). TIL levels in HER-2-positive BC patients were positively correlated with both HER-2 and CD8 expression. TIL levels were closely related to the prognosis of BC patients, which may provide a theoretical basis for precision treatment in BC.
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