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脑膜瘤患者肿瘤中CD44的蛋白表达:与临床病理参数及生存的关联

Protein expression of CD44 in patients with meningioma tumors: association with clinicopathological parameters and survival.

作者信息

Trivedi Trupti, Bhalala Neha, Dialani Kirti, Trivedi Priti

机构信息

Molecular Diagnostics and Research Laboratory I, Cancer Biology Department, The Gujarat Cancer & Research Institute, Asarwa, Ahmedabad, Gujarat, 380 016, India.

Department of Oncopathology, The Gujarat Cancer & Research Institute, Ahmedabad, Gujarat, India.

出版信息

J Egypt Natl Canc Inst. 2024 Dec 27;36(1):43. doi: 10.1186/s43046-024-00249-9.

Abstract

OBJECTIVE

Meningiomas are a molecularly ill-defined heterogeneous group of indolent intracranial tumors. Though, WHO grade 1 tumors are histologically benign, sometimes they transform into malignant and may be recurrent which remains always challenging to clinicians. Therefore, the current study sought to discover the clinical relevance of CD44 in meningioma patients.

METHOD

Protein expression of CD44 was investigated using immunohistochemistry in a total of 70 meningioma patients. Immunoscore performed using modified H-score, CD44 expression correlated with clinicopathological parameters and progression-free survival (PFS) and overall survival (OS). Univariate and multivariate survival analysis was analyzed. The data was evaluated using SPSS statistical software and P-value ≤ 0.05 was considered as significant.

RESULTS

The membranous and cytoplasmic protein expression of CD44 was noted in meningioma tumors. Based on H-score, the weak (0-190 score) and strong (191-300 score) immunoreactivity was observed in 62.9% and 37.1% of patients, respectively. A statistically significant positive correlation was found between strong CD44 expression and WHO grade 2/3 tumors (χ = 33.551, r = + 0.692, P = 0.0001), and with the presence of brain invasion (χ = 19.521, r = + 0.528, P = 0.001). In Kaplan-Meier univariate survival analysis for PFS and OS, apart from WHO grade of tumors (PFS; log-rank = 12.309, P = 0.0001, OS; log-rank = 17.830, P = 0.0001) and brain invasion status (PFS; log-rank = 11.941, P = 0.001, OS; log-rank = 13.554, P = 0.0001) CD44 expression (PFS; log-rank = 14.942, P = 0.0001, OS; log-rank = 20.986, P = 0.0001) remained significant prognostic factor for PFS and OS. In multivariate survival analysis, at step 1, only CD44 remained independent prognosticator for PFS (HR = 11.014, 95% CI = 2.256-23.602, P = 0.001) and OS (HR = 8.553, 95% CI = 2.831-25.847, P = 0.0001). In relation to treatment offered, patients with strong CD44 expression and if treated with surgery followed by adjuvant radiotherapy showed a high incidence of death (log-rank = 13.402, P = 0.0001) as compared to patients treated with surgery only. Receiver operating characteristic (ROC) curves also confirmed a good efficacy of CD44 as a prognosticator for disease outcome (PFS; P = 0.0001, OS; P = 0001).

CONCLUSION

Our overall findings addressed that a study of CD44 protein expression would be beneficiated to meningioma patients from unnecessary overtreatment and drug-induced toxicity. Also, CD44 could be one of the promising biomarkers that might differentiate high-risk meningioma patients for better treatment management.

摘要

目的

脑膜瘤是一组分子特征不明确的惰性颅内肿瘤。虽然世界卫生组织(WHO)1级肿瘤在组织学上是良性的,但有时会转变为恶性,且可能复发,这对临床医生来说始终是一项挑战。因此,本研究旨在探索CD44在脑膜瘤患者中的临床相关性。

方法

采用免疫组织化学方法对70例脑膜瘤患者的CD44蛋白表达进行研究。使用改良的H评分进行免疫评分,分析CD44表达与临床病理参数、无进展生存期(PFS)和总生存期(OS)的相关性。进行单因素和多因素生存分析。数据使用SPSS统计软件进行评估,P值≤0.05被认为具有统计学意义。

结果

在脑膜瘤肿瘤中观察到CD44的膜性和细胞质蛋白表达。基于H评分,分别在62.9%和37.1%的患者中观察到弱(0 - 190分)和强(191 - 300分)免疫反应性。发现CD44强表达与WHO 2/3级肿瘤(χ = 33.551,r = +0.692,P = 0.0001)以及脑侵袭的存在(χ = 19.521,r = +0.528,P = 0.001)之间存在统计学显著的正相关。在PFS和OS的Kaplan - Meier单因素生存分析中,除了肿瘤的WHO分级(PFS;对数秩 = 12.309,P = 0.0001,OS;对数秩 = 17.830,P = 0.0001)和脑侵袭状态(PFS;对数秩 = 11.941,P = 0.001,OS;对数秩 = 13.554,P = 0.0001)外,CD44表达(PFS;对数秩 = 14.942,P = 0.0001,OS;对数秩 = 20.986,P = 0.0001)仍然是PFS和OS的显著预后因素。在多因素生存分析中,在第一步,只有CD44仍然是PFS(HR = 11.014,95%CI = 2.256 - 23.602,P = 0.001)和OS(HR = 8.553,95%CI = 2.831 - 25.847,P = 0.0001)的独立预后指标。关于所提供的治疗,与仅接受手术治疗的患者相比,CD44强表达且接受手术加辅助放疗的患者死亡发生率较高(对数秩 = 13.402,P = 0.0001)。受试者工作特征(ROC)曲线也证实CD44作为疾病预后指标具有良好的效能(PFS;P = 0.0001,OS;P = 0001)。

结论

我们的总体研究结果表明,对CD44蛋白表达的研究将使脑膜瘤患者受益,避免不必要的过度治疗和药物诱导的毒性。此外,CD44可能是有前景的生物标志物之一,可用于区分高危脑膜瘤患者以进行更好的治疗管理。

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