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Ki-67和降钙素原表达水平对预测肝移植后肝细胞癌的生物学行为是否有用?

Are Ki-67 and Procalcitonin Expression Levels Useful in Predicting the Biological Behavior of Hepatocellular Carcinoma After Liver Transplantation?

作者信息

Karabulut Ertugrul, Akbulut Sami, Samdanci Emine Turkmen, Akatli Ayse Nur, Elsarawy Ahmed, Kucukakcali Zeynep, Ogut Zeki, Tuncer Adem, Ince Volkan, Yilmaz Sezai

机构信息

Department of Surgery and Liver Transplant Institute, Faculty of Medicine, Inonu University, 44280 Malatya, Turkey.

Department of Biostatistics and Medical Informatics, Faculty of Medicine, Inonu University, 44280 Malatya, Turkey.

出版信息

J Clin Med. 2024 Dec 30;14(1):144. doi: 10.3390/jcm14010144.

Abstract

: Examinations of procalcitonin (PCT) and Ki-67 expression levels in hepatocellular carcinoma (HCC) patients who have undergone liver transplantation (LT) through immunohistochemical analyses of tumor tissue may reveal the biological characteristics of the tumor, thus informing the selection of HCC patients for LT. : Hepatectomy specimens from 86 HCC patients who underwent LT were obtained and analyzed immunohistochemically for the expression of PCT and Ki-67. The percentage and intensity of PCT staining, as well as the percentage of Ki-67 expression, were assessed for each patient. The impacts of PCT and Ki-67 expression on disease-free survival, overall survival, and the recurrence rate were studied, as well as their correlations with other clinicopathological features. : The recurrent HCC group showed a higher Ki-67 level ( < 0.001), larger maximum dominant tumor diameter ( < 0.001), and higher rate of vascular invasion ( = 0.001). The pre-transplant AFP ( = 0.001), maximum dominant tumor diameter ( < 0.001), number of tumor nodules ( < 0.001), rate of vascular invasion ( = 0.001), and Ki-67 level ( = 0.044) were higher in patients beyond the Milan criteria. Similarly, the pre-transplant AFP ( < 0.001); maximum dominant tumor diameter ( < 0.001); number of tumor nodules ( < 0.001); rates of portal vein tumor thrombus ( = 0.002), poor differentiation ( = 0.021), and vascular invasion ( < 0.001); and Ki-67 level ( = 0.010) were higher in patients beyond the expanded Malatya criteria. The maximum dominant tumor diameter ( = 0.006); Ki-67 level ( = 0.003); rates of vascular invasion ( < 0.001), cases beyond the Milan criteria ( = 0.042) and the expanded Malatya criteria ( = 0.027), and portal vein tumor thrombus ( = 0.020); and presence of recurrence ( < 0.001) were higher in HCC patients with mortality. The Kaplan-Meier estimates indicated that Ki-67 levels exceeding 5% significantly affected DFS and OS. Although the Kaplan-Meier estimates indicated that a PCT staining percentage of ≥25% did not have a statistically significant effect on DFS or OS, the outcomes may be considered clinically significant. : This study demonstrated that the Ki-67 proliferation index can be used as a predictive biomarker of the biological behavior of HCC. Furthermore, we claim that PCT expression over a particular threshold might impact recurrence and survival, and we believe that further multicenter prospective studies focused on standardized PCT antibody staining are crucial in order to determine its potential as a biomarker for HCC.

摘要

通过对肿瘤组织进行免疫组化分析,检测接受肝移植(LT)的肝细胞癌(HCC)患者的降钙素原(PCT)和Ki-67表达水平,可能揭示肿瘤的生物学特征,从而为HCC患者LT的选择提供依据。

获取86例接受LT的HCC患者的肝切除标本,进行免疫组化分析以检测PCT和Ki-67的表达。评估每位患者PCT染色的百分比和强度以及Ki-67表达的百分比。研究PCT和Ki-67表达对无病生存期、总生存期和复发率的影响,以及它们与其他临床病理特征的相关性。

复发性HCC组的Ki-67水平较高(<0.001),最大优势肿瘤直径较大(<0.001),血管侵犯率较高(=0.001)。米兰标准以外的患者移植前甲胎蛋白(AFP)水平(=0.001)、最大优势肿瘤直径(<0.001)、肿瘤结节数量(<0.001)、血管侵犯率(=0.001)和Ki-67水平(=0.044)较高。同样,扩大的马拉蒂亚标准以外的患者移植前AFP水平(<0.001)、最大优势肿瘤直径(<0.001)、肿瘤结节数量(<0.001)、门静脉肿瘤血栓形成率(=0.002)、低分化率(=0.021)和血管侵犯率(<0.001)以及Ki-67水平(=0.010)较高。有死亡的HCC患者的最大优势肿瘤直径(=0.006)、Ki-67水平(=0.003)、血管侵犯率(<0.001)、米兰标准以外的病例数(=0.042)和扩大的马拉蒂亚标准以外的病例数(=0.027)以及门静脉肿瘤血栓形成率(=0.020)和复发率(<0.001)较高。Kaplan-Meier估计表明,Ki-67水平超过5%对无病生存期和总生存期有显著影响。虽然Kaplan-Meier估计表明PCT染色百分比≥25%对无病生存期或总生存期没有统计学显著影响,但这些结果可能具有临床意义。

本研究表明,Ki-67增殖指数可作为HCC生物学行为的预测生物标志物。此外,我们认为PCT在特定阈值以上的表达可能影响复发和生存,并且我们相信,为了确定其作为HCC生物标志物的潜力,进一步开展专注于标准化PCT抗体染色的多中心前瞻性研究至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28e2/11720816/3fea80493d26/jcm-14-00144-g001a.jpg

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