肝细胞癌组织中Glypican-3表达与肿瘤生物学行为的关系

摘要/Abstract

摘要： 目的探讨肝细胞癌组织中磷脂酰肌醇蛋白聚糖3(GPC3)表达与肝细胞癌恶性生物学行为之间的关系。方法回顾性分析2017年12月至2020年8月昆明市第三人民医院就诊的77例肝细胞癌患者的临床资料,所有组织标本均来源于术中切除组织,其中肝细胞癌标本取自于肝细胞癌原发病灶处,癌旁组织取自于距离原发病灶5 cm的癌旁肝组织,正常肝组织取自于距离肝细胞癌原发病灶5 cm外的肝组织。比较不同肝组织中GPC3表达情况,并分析GPC3表达与肝细胞癌癌细胞恶性生物学行为[增殖基因包括:沉默信息调节因子6(SIRT6)、叉头框P2(FOXP2)、缺氧诱导因子-1α(HIF-1α);肝细胞凋亡相关因子包括:磷脂肌醇-3-激酶(PI3K)、含半胱氨酸的天冬氨酸蛋白水解酶3(caspase-3)、丝苏氨酸蛋白激酶(Akt)]之间的关系。结果肝细胞癌组织中GPC3阳性表达率为98.70%(76/77),癌旁组织为89.61%(69/77),正常组织为2.60%(2/77),差异有统计学意义(χ²=275.074,P<0.01),其中正常肝组织GPC3阳性表达率低于癌旁组织,差异有统计学意义(χ²=10.421,P=0.004);正常肝组织GPC3阳性表达率低于肝细胞癌组织,差异有统计学意义(χ²=11.645,P<0.01);各组织中S100A2表达分级比较差异有统计学意义(Z=6.839,P<0.01);与癌旁组织相比,肝细胞癌组织中GPC3分值、STC2、FOXP2、HIF-1α、SIRT6、PI3K、caspase-3、Akt表达均较高,差异有统计学意义(P<0.05);经双变量Pearson直线相关性检验结果显示,肝细胞癌组织中GPC3表达与SIRT6、FOXP、HIF-1α、PI3K、caspase-3、Akt表达均呈正相关(r＞0,P<0.05)。结论肝细胞癌组织中GPC3表达与癌细胞生物学行为之间关系密切,临床可考虑将GPC3作为肝细胞癌治疗的新靶点。

关键词: 肝细胞癌, 磷脂酰肌醇蛋白聚糖3, 肿瘤, 生物学行为, 相关性

Abstract: Objective To guide the early diagnosis and treatment of hepatocellular carcinoma (HCC) through investigating the relationship between phosphatidylinositol proteoglycan 3 (GPC3) expression and malignant biological behavior of HCC.Methods The clinical data of 77 patients with HCC admitted to our hospital from December 2017 to August 2020 were retrospectively analyzed. All specimens were obtained from intraoperative pathologically resected tissues, HCC specimens were resected from the primary lesion, pericarcinomatous tissue was resected from the cancer adjacent liver tissues which was 5 cm away from the primary lesion, and normal liver tissue confirmed by pathology was resected from more than 5 cm away from the primary lesion. The GPC3 expression situations of different liver tissues were compared and the correlation between them and malignan biological behavior of HCC cells was analyzed [proliferation genes including: silent information regulator 6 (SIRT6), forkhead box P2 (FOXP2), hypoxia-inducible factor-1α (HIF-1α); hepatocyte apoptosis-related factors: phosphatidylinositol-3-kinase (PI3K), cysteine-containing aspartate protein hydrolase 3 (caspase-3), and serine threonine protein kinase (Akt)].Results The positive expression rates of GPC3 in HCC tissues, pericarcinomatous tissue normal tissues were 98.70% (76/77), 89.61% (69/77) and 2.60% (2/77) respectively, and the difference was statistically significant (χ²=275.074, P<0.001). The positive rate of GPC3 in normal liver tissues was significantly lower than that in pericarcinomatous tissue, (Z=10.421, P=0.004) and HCC tissues (Z=11.645, P<0.001). There was no significant difference of S100A2 expression grade among the different tissues (Z=6.839, P<0.001). Compared with pericarcinomatous tissue, the expression levels of GPC3, STC2, FOXP2, HIF-1α, SIRT6, PI3K, caspase-3 and Akt were higher in HCC tissues, the differences were statistically significant (P<0.05). Bivariate Pearson linear correlation test showed that GPC3 expressed in HCC tissues was positively associated with malignant biological behavior of cancer cells (proliferation genes: SIRT6, FOXP, HIF-1α; apoptosis-related factors: PI3K,caspase-3, Akt) (r>0, P<0.05).Conclusion There is a close relationship between GPC3 expression in HCC tissues and the biological behavior of cancer cells. GPC3 can be considered as a new target for HCC treatment, aimed at guiding the therapy of patients with HCC and improve prognosis.

Key words: Hepatocellular carcinoma, Phosphatidylinositol proteoglycan 3, Tumor, Biological behavior, Correlation

常丽仙, 刘春云, 谢翩. 肝细胞癌组织中Glypican-3表达与肿瘤生物学行为的关系[J]. 肝脏, 2022, 27(3): 284-287.

CHANG Li-xian, LIU Chun-yun, XIE Pian. Relationship between Glypican-3 expression level and tumor biological behavior in hepatocellular carcinoma tissues[J]. Chinese Hepatolgy, 2022, 27(3): 284-287.

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