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摘要：
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摘要：目的 探讨原发性肝癌患者四跨膜蛋白8（tetraspanin-8，Tspan8）、埃兹蛋白（Ezrin）及微小
RNA-634（microRNA-634，miR-634）水平与预后的相关性。方法 选取2012年2月至2013年2月于天
门市第一人民医院住院的120例原发性肝癌患者为研究对象，记录患者体重指数（body mass index，
BMI）、肝癌组织分化程度、TNM分期、肝内转移及淋巴结转移等。采用免疫组织化学法检测肝癌
组织和癌旁组织Tspan8和Ezrin表达水平，采用酶联免疫吸附法检测甲胎蛋白（α-fetoprotein，AFP）
水平，采用实时荧光定量聚合酶链反应（quantitative real-time polymerase chain reaction，qRT-PCR）
检测miR-634相对表达量。采用Spearman相关性分析肝癌组织分化程度、TNM分期、肝内转移及淋巴
结转移与肝癌组织Tspan8、Ezrin、miR-634水平的相关性，采用Pearson相关性分析肝癌组织Tspan8、
miR-634、Ezrin水平与AFP的相关性，采用Cox回归分析患者5年生存的危险因素。结果 肝癌组织
Tspan8 [（1.76 ± 0.14）% vs（0.23 ± 0.03）%]和Ezrin [（1.97 ± 0.22）% vs（1.28 ± 0.17）%]显著高于
癌旁组织，miR-634相对表达量显著低于癌旁组织（0.25 ± 0.03 vs 1.11 ± 0.23），差异均有统计学意
义（t值分别为117.059、27.186、40.616，P均＜ 0.001）。不同肝癌组织分化程度 [低分化vs中、高分
化：Tspan8（1.64 ± 0.28）% vs（1.93 ± 0.24）%，Ezrin（1.88 ± 0.21）% vs（1.99 ± 0.28）%，miR-634 0.33 ±
0.05 vs 0.21 ± 0.07]、TNM分期 [Ⅰ～Ⅱ期vs Ⅲ～Ⅳ期：Tspan8（1.63 ± 0.46）% vs（1.92 ± 0.19）%，
Ezrin（1.64 ± 0.33）% vs（2.12 ± 0.45）%，miR-634 0.33 ± 0.09 vs 0.15 ± 0.03]、淋巴结转移 [有vs无：
Tspan8（1.94 ± 0.12）% vs（1.60 ± 0.16）%，Ezrin（2.03 ± 0.52）% vs（1.68 ± 0.39）%，miR-634 0.22 ±
0.08 vs 0.32 ± 0.04] 及肝内转移 [有vs无：Tspan8（1.94 ± 0.52）% vs（0.62 ± 0.03）%，Ezrin（1.99 ±
0.45）% vs（1.77 ± 0.33）%，miR-634 0.22 ± 0.07 vs 0.35 ± 0.03] 原发性肝癌患者的Tspan8、Ezrin及
miR-634差异有统计学意义（P均＜ 0.05）。患者肝癌组织分化程度、TNM分期、肝内转移及淋巴结转
移分别与Tspan8和Ezrin呈正相关（r s ＞ 0.1，P ＜ 0.05），与miR-634呈负相关（r s ＜ -0.2，P ＜ 0.05）。
Tspan8、Ezrin表达水平与AFP呈正相关（r = 0.87，P = 0.012；r = 0.91，P = 0.006），miR-634相对表达量
与AFP呈负相关（r = -0.92，P = 0.0001）。Cox回归分析表明，年龄≥ 55岁、存在淋巴结转移、Tspan8
及Ezrin是患者5年生存的独立危险因素，miR-634是患者5年生存的独立保护因素。结论 原发性肝癌患
者的不良结局与Tspan8和Ezrin呈正相关，与miR-634呈负相关。
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Abstract: Objective To investigate the relationship among the expression of tetraspanin-8 (Tspan8), Ezrin,
microRNA-634 (miR-634) and prognosis of patients with primary liver cancer. Methods Total of 120
patients with primary liver cancer in the First People’s Hospital of Tianmen from February 2012 to February
2013 were selected. Body mass index (BMI), differentiation degree of liver cancer, TNM stage, intrahepatic
metastasis and lymph node metastasis were recorded. Immunohistochemistry method was used to detect the
expression levels of Tspan8 and Ezrin. Enzyme-linked immunosorbent assay was used to detect the level
of α-fetoprotein (AFP). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the
relative expression of miR-634. Spearman correlation analysis was used to analyze the correlation between
the differentiation degree, TNM stage, intrahepatic metastasis and lymph node metastasis and the levels
of tspan8, ezrin and miR-634 in liver cancer tissue. Pearson correlation analysis was used to analyze the
correlation between the levels of tspan8, mir-634 and ezrin and AFP in paracancerous tissue. Cox regression
analysis was used to analyze the risk factors of 5-year survival. Results The levels of Tspan8 [(1.76 ± 0.14)%
vs (0.23 ± 0.03)%] and Ezrin [(1.97 ± 0.22)% vs (1.28 ± 0.17)%] in liver cancer tissues were significantly
higher and the relative expression of miR-634 were significantly lower (0.25 ± 0.03 vs 1.11 ± 0.23) than
those in paracancerous tissues, the differences were statistically significant (t = 117.059, 27.186, 40.616; all
P ＜ 0.001). Different differentiation degree of liver cancer tissue [low differentiation vs medium and high
differentiation: Tspan8 (1.64 ± 0.28)% vs (1.93 ± 0.24)%, Ezrin (1.88 ± 0.21)% vs (1.99 ± 0.28)%, miR-634
0.33 ± 0.05 vs 0.21 ± 0.07], TNM stage [Ⅰ～Ⅱ stage vs Ⅲ～Ⅳstage: Tspans8 (1.63 ± 0.46)% vs (1.92 ± 0.19)%,
Ezrin (1.64 ± 0.33) vs (2.12 ± 0.45)%, miR-634 0.33 ± 0.09 vs 0.15 ± 0.03], lymph node metastasis [with vs
without: Tspan8 (1.94 ± 0.12)% vs (1.60 ± 0.16)%, Ezrin (2.03 ± 0.52)% vs (1.68 ± 0.39)%, miR-634
0.22 ± 0.08 vs 0.32 ± 0.04) and intrahepatic metastasis [with vs without: Tspan8 (1.94 ± 0.52)% vs (0.62 ± 0.03)%,
Ezrin (1.99 ± 0.45) vs (1.77 ± 0.33)%, miR-634 0.22 ± 0.07 vs 0.35 ± 0.03] of patients with primary liver cancer
were statistically significant (all P ＜ 0.05). The differentiation degree of liver cancer tissue, TNM staging,
liver metastasis and lymph node metastasis were positively correlated with Tspan8 and Ezrin (r s ＞ 0.1, P ＜ 0.05),
and were negatively correlated with miR-634 (r s ＜ -0.2, P ＜ 0.05). The expression of tspan8 and Ezrin were
positively correlated with AFP (r = 0.87, P = 0.012; r = 0.91, P = 0.006), while the relative expression of miR-
634 was negatively correlated with AFP (r = -0.92, P = 0.0001). Cox regression analysis showed that ≥ 55 years
old, lymph node metastasis, tspan8 and Ezrin were independent risk factors for 5-year survival, and miR-
634 was an independent protective factor for 5-year survival. Conclusions The adverse outcomes of patients
with primary liver cancer were positively correlated with levels of Tspan 8 and Ezrin and were negatively
correlated with the relative expression of miR-634.
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