CD133 expression and α-fetoprotein levels define novel prognostic subtypes of HBV-associated hepatocellular carcinoma: A long-term follow-up analysis.
CD133 expression and α-fetoprotein levels define novel prognostic subtypes of HBV-associated hepatocellular carcinoma: A long-term follow-up analysis.
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CD133表达和α-毒素水平定义了与HBV相关的肝细胞癌的新型预后亚型：长期随访分析。
DOI：
10.3892/ol.2017.7704
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发表时间：
2018-03
期刊：
影响因子：
2.9
通讯作者：
Zhang T
中科院分区：
文献类型：
--
作者：
Dai XM;Yang SL;Zheng XM;Chen GG;Chen J;Zhang T
肝细胞癌（HCC）是一种高度异质性的肿瘤，其可能由特定HCC细胞的干/祖细胞特征引起。最近的研究已经根据一个与干细胞相关的标志物将HCC细分为不同的预后亚型。然而，一个与干细胞相关的标记物不足以清楚地定义癌症干细胞，也不足以解释HCC的异质性。对于预后应用的更精确的亚型分类，需要多个干性相关标志物的组合。分化抗原133（CD 133）和甲胎蛋白（AFP）是HCC常见的干细胞相关标志物，但尚未用于HCC亚型分类。在本研究中，CD 133的表达进行了评估，免疫组化在127例B病毒相关的肝癌肿瘤标本。根据CD 133免疫组化染色和血清AFP水平，HCC病例可分为四种亚型，表现出不同的临床病理特征和不同的预后。4种亚型之间，肿瘤病灶数目、组织学分级和血管浸润差异有统计学意义（分别为P=0.002、P=0.018和P=0.022）。CD 133 +AFP+ HCC与相对较差的预后相关，CD 133 −AFP− HCC与相对较好的预后相关，而CD 133 +AFP− HCC和CD 133 −AFP+ HCC与中等预后相关。这些预后值通过临界值或统计学显著性得到证实（所有组之间，总生存期，P=0.061;无复发生存期，P=0.015）。这些结果定义了一个新的和简单的系统，根据CD 133和AFP，HCC分为四个不同的预后亚型。该分类系统可能有助于评估HCC患者的个性化治疗。
Hepatocellular carcinoma (HCC) is a highly heterogeneous type of tumor, which may be caused by the stem/progenitor cell features of particular HCC cells. Recent studies have subclassified HCC into different prognostic subtypes according to just one stemness-associated marker. However, one stemness-associated marker is not sufficient to clearly define cancer stem cells, or to decipher the heterogeneous nature of HCC. For a more precise subtype classification for prognostic application, a combination of multiple stemness-associated markers is required. Cluster of differentiation 133 (CD133) and α-fetoprotein (AFP) are common stemness-associated markers for HCC that have not yet been employed for HCC subtype classification. In the present study, CD133 expression was assessed by immunohistochemistry in 127 hepatitis B virus-associated HCC tumor specimens. Based on CD133 immunostaining and serum AFP levels, the HCC cases were subclassified into four subtypes, which demonstrated different clinicopathological features and varying prognoses. Among the four subtypes, the number of tumor lesions, histological grade and vascular invasion were significantly different (P=0.002, P=0.018 and P=0.022, respectively). CD133+AFP+ HCC was associated with a relatively poor prognosis, CD133−AFP− HCC was associated with a relatively good prognosis, while CD133+AFP− HCC and CD133−AFP+ HCC were associated with an intermediate prognosis. These prognostic values were confirmed by borderline or statistical significance (between all groups, overall survival, P=0.061; recurrence-free survival, P=0.015). These results define a novel and simple system, based on CD133 and AFP, for classifying HCC into four distinct prognostic subtypes. This classification system may aid the assessment of patients with HCC for personalized therapy.
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