Rozeik Mohammed Saeed, Hammam Olfat Ali, Ali Ali Ibrahim, Magdy Mona, Khalil Heba, Anas Amgad, Abo El Hassan Ahmed Abdelaleem, Rahim Ali Abdel, El-Shabasy Ahmed Ibrahim
M.D., Tropical Medicine Department, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
M.D., Pathology Department, Theodor Bilharz Research Institute, Imbaba, Giza, Egypt.
Electron Physician. 2017 Jul 25;9(7):4708-4717. doi: 10.19082/4708. eCollection 2017 Jul.
Cancer stem cells (CSCs) play a critical role in tumor development, progression, metastasis and recurrence.
To evaluate hepatic expression of CD44 and CD133 in Egyptian patients with HCV-induced chronic liver diseases and hepatocellular carcinomas (HCCs), and to assess its correlation with inflammatory activity scores, stages of fibrosis (in chronic hepatitis with or without cirrhosis) and grades of HCC.
This prospective case-control study was conducted on eighty subjects who attended the Tropical Diseases Department, Al-Azhar University Hospital, and in collaboration with Theodor Bilharz Research Institute (2014-2016). They were divided as follows: A) Control healthy group: Ten individuals with serologically negative HCV-Ab and HBsAg, and histopathologically normal liver, B) Seventy patients subdivided into 3 groups; Twenty subjects each, as: HCV-Ab+ non-cirrhotic, HCV-Ab+ cirrhotic and HCC. Necroinflammatory activity and fibrosis in non-neoplastic liver biopsies were scored according to the METAVIR scoring system. CD44 and CD133 immunostaining was evaluated in all groups semi-quantitatively using H score. Statistical analysis was performed by SPSS version 22, using independent-samples t-test.
Our study showed a significant increase of mean CD44 & CD133 expression values with disease progression among the groups (p<0.05). Their expressions increased significantly with the inflammatory activity scores and stages of fibrosis, reaching the highest values in A3F4 score compared to A1F1 (p<0.05). Moreover, there was a significant increase of their expressions across HCC grades (p<0.05), however with no significant correlation with focal lesions size.
CSCs clusters exhibiting CD133+ and/or CD44+ profiles were identified in chronic hepatitis, liver cirrhosis and HCC. CD133 and CD44 expressions significantly corresponded to the increased inflammatory activity, fibrosis stages and higher tumor grades. Therefore, evaluation of CD44 and CD133 expression profiles as CSCs markers in non-neoplastic liver and HCCs can help in development of novel therapeutic agents for HCC targeting and prevention.
癌症干细胞（CSCs）在肿瘤的发生、发展、转移和复发中起着关键作用。
评估埃及丙型肝炎病毒（HCV）诱导的慢性肝病和肝细胞癌（HCC）患者肝脏中CD44和CD133的表达，并评估其与炎症活动评分、纤维化阶段（伴有或不伴有肝硬化的慢性肝炎）和HCC分级的相关性。
这项前瞻性病例对照研究在艾资哈尔大学医院热带病科就诊的80名受试者中进行，并与 Theodor Bilharz 研究所合作（2014 - 2016年）。他们被分为以下几组：A）健康对照组：10名 HCV - Ab 和 HBsAg 血清学阴性且肝脏组织病理学正常的个体；B）70名患者分为3组，每组20名，分别为：HCV - Ab 阳性非肝硬化组、HCV - Ab 阳性肝硬化组和 HCC 组。非肿瘤性肝活检中的坏死性炎症活动和纤维化根据 METAVIR 评分系统进行评分。所有组均使用 H 评分对 CD44 和 CD133 免疫染色进行半定量评估。使用 SPSS 22版进行统计分析，采用独立样本 t 检验。
我们的研究表明，随着疾病进展，各组中 CD44 和 CD133 的平均表达值显著增加（p < 0.05）。它们的表达随着炎症活动评分和纤维化阶段显著增加，与 A1F1 相比，在 A3F4 评分时达到最高值（p < 0.05）。此外，它们的表达在 HCC 分级中显著增加（p < 0.05），但与局灶性病变大小无显著相关性。
在慢性肝炎、肝硬化和 HCC 中鉴定出了表现为 CD133 + 和/或 CD44 + 特征的癌症干细胞簇。CD133 和 CD44 的表达与炎症活动增加、纤维化阶段和更高的肿瘤分级显著相关。因此，评估非肿瘤性肝脏和 HCC 中作为癌症干细胞标志物的 CD44 和 CD133 表达谱有助于开发针对 HCC 的新型治疗药物和预防措施。
