Department of Biochemistry & Molecular Biology, Chang-Gung University, Taoyuan, Taiwan 333, Republic of China.
Gynecol Oncol. 2011 Jan;120(1):135-44. doi: 10.1016/j.ygyno.2010.10.005. Epub 2010 Oct 28.
Cervical carcinoma is the second most common cause of death from gynecological cancers worldwide. Knowledge of the molecular mechanisms underlying the tumorigenesis of cervical cancer cell, except human papilloma virus infection, is limited.
A microarray was used to study the differential expression of genes in cancerous tissues to identify new molecular markers for diagnosis and prognosis. Their differential expression was confirmed with Western blotting and immunohistochemical analyses. The clinical correlations and prognostic significance of the aberrantly expressed proteins were evaluated to identify novel biomarkers of cervical cancer.
The expression of gelsolin was significantly upregulated in 78% of patients with cervical cancer, and gelsolin was selected for further study. Gelsolin expression was stronger in cervical tumor tissues than in the surrounding noncancerous tissues (P<0.001). Gelsolin expression in the plasma of cervical cancer patients was increased 2.2-fold compared with that of healthy control subjects (P<0.001). The levels of plasma gelsolin in the early and late stages were significantly different (P=0.006). According to immunohistochemical analysis, increased gelsolin expression was associated with histological type and FIGO stage II. The 5-year overall survival and recurrence-free survival rates for the low-expression group (cut-off=115) were significantly higher than those of the high-expression group. Cancer cells with reduced gelsolin expression exhibited reduced migration and proliferation.
These results provide strong evidence that gelsolin plays an important role in cellular proliferation and migration in cervical cancer and suggest that gelsolin is a promising marker for cervical cancer screening and prognosis.
宫颈癌是全球妇科癌症死亡的第二大主要原因。除了人乳头瘤病毒感染外，对宫颈癌发生的分子机制知之甚少。
采用微阵列技术研究癌症组织中基因的差异表达，以鉴定新的分子标志物用于诊断和预后。通过 Western blot 和免疫组织化学分析证实其差异表达。评估异常表达蛋白的临床相关性和预后意义，以鉴定宫颈癌的新型生物标志物。
在 78%的宫颈癌患者中，gelsolin 的表达明显上调，因此选择 gelsolin 进行进一步研究。宫颈肿瘤组织中的 gelsolin 表达明显强于周围非癌组织（P<0.001）。与健康对照组相比，宫颈癌患者血浆中的 gelsolin 表达增加了 2.2 倍（P<0.001）。早期和晚期血浆 gelsolin 水平差异显著（P=0.006）。根据免疫组织化学分析，gelsolin 表达增加与组织学类型和 FIGO 分期 II 相关。低表达组（cut-off=115）的 5 年总生存率和无复发生存率明显高于高表达组。gelsolin 表达降低的癌细胞迁移和增殖能力降低。
这些结果为 gelsolin 在宫颈癌细胞增殖和迁移中发挥重要作用提供了有力证据，并表明 gelsolin 是宫颈癌筛查和预后的有前途的标志物。
