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环孢素 A 配体和受体 CD147 与舌鳞癌缺氧、血管生成、转移和预后的关系。

Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinoma.

机构信息

The State Key Laboratory Breeding Base of Basic Science of Stomatology, Hubei Province and Key Laboratory of Oral Biomedicine (Wuhan University), Ministry of Education, China.

出版信息

Histopathology. 2012 Apr;60(5):793-803. doi: 10.1111/j.1365-2559.2011.04130.x. Epub 2012 Feb 9.

Abstract

AIMS

We evaluated the association of ligand cyclophilin A (CypA) and receptor CD147 with hypoxia, angiogenesis, lymph node metastasis and prognosis of patients with tongue squamous cell carcinoma (TSCC).

METHODS AND RESULTS

We studied the expression of CypA, CD147, hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor A and C (VEGF-A and VEGF-C) protein by immunohistochemistry in 80 specimens of TSCC. CypA, CD147, HIF-1α, VEGF-A and VEGF-C were overexpressed in TSCCs, and were significantly higher than those in normal oral mucosa tissues (P<0.01). Increased ligand CypA and receptor CD147 correlated significantly with expression of HIF-1α, VEGF-A and VEGF-C. A significant relationship between VEGF-A and VEGF-C was also detected (P<0.01). Patients with overexpression of CypA, CD147, HIF-1α and VEGF-C had significantly worse overall survival (P<0.05) using Kaplan-Meier analysis. Multivariate Cox regression analysis showed that HIF-1α, recurrence and distant metastasis were independent prognostic factors on overall survival in TSCC patients.

CONCLUSIONS

The association of expression of ligand CypA and receptor CD147 with carcinogenesis, hypoxia, angiogenesis, metastasis and prognosis of TSCC suggests that ligand CypA and receptor CD147 may have prognostic value and could be regarded as potential therapeutic targets in TSCC.

摘要

目的

我们评估配体亲环素 A(CypA)和受体 CD147 与舌鳞状细胞癌(TSCC)患者的缺氧、血管生成、淋巴结转移和预后的关系。

方法和结果

我们通过免疫组织化学方法研究了 80 例 TSCC 标本中 CypA、CD147、缺氧诱导因子 1α(HIF-1α)、血管内皮生长因子 A 和 C(VEGF-A 和 VEGF-C)蛋白的表达。CypA、CD147、HIF-1α、VEGF-A 和 VEGF-C 在 TSCC 中过度表达,明显高于正常口腔黏膜组织(P<0.01)。配体 CypA 和受体 CD147 的增加与 HIF-1α、VEGF-A 和 VEGF-C 的表达显著相关。还检测到 VEGF-A 和 VEGF-C 之间存在显著关系(P<0.01)。Kaplan-Meier 分析显示,CypA、CD147、HIF-1α 和 VEGF-C 过度表达的患者总生存率显著降低(P<0.05)。多变量 Cox 回归分析显示,HIF-1α、复发和远处转移是 TSCC 患者总生存率的独立预后因素。

结论

配体 CypA 和受体 CD147 的表达与 TSCC 的发生、缺氧、血管生成、转移和预后相关,表明配体 CypA 和受体 CD147 可能具有预后价值,并可作为 TSCC 的潜在治疗靶点。

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