Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji 133002, China.
Department of Pathology, Yanbian Women's Hospital, Yanji 133000, China.
Hum Pathol. 2018 May;75:179-188. doi: 10.1016/j.humpath.2018.02.006. Epub 2018 Feb 13.
T lymphoma invasion and metastasis 1 (Tiam1), a guanine nucleotide exchange factor, is involved in the tumorigenesis of a number of malignancies. This study was aimed to explore the role of Tiam1 in cervical cancer progression, and evaluate the prognostic values. Tiam1 protein expression levels were detected by immunohistochemical (IHC) staining in 174 cervical cancer tissues, 92 of CINs (cervical intraepithelial neoplasia) and 32 of normal cervical epithelia tissues. Clinicopathological parameters and overall survival data were collected and compared between different Tiam1 statuses. The role of Tiam1 in cervical cancer proliferation, migration and angiogenesis were detected using si-RNA (small interfering RNA) transfection. In results, Tiam1 protein showed a cytoplasmic and nuclear staining pattern in cervical cancer tissues. The strongly positive expression of Tiam1 protein was observed in 51.72% (90/174) of cervical cancers, which was significantly higher than in CINs and normal cervical epithelia tissues (9.38%, 3/32). High Tiam1 protein expression was closely associated with advanced clinical stage, differentiation, lymph node (LN) metastasis, HPV infection and lower overall survival (OS) rates in cervical cancer. Multivariate analysis indicated that Tiam1 was an independent prognostic factor, along with clinical stage, in patients with cervical cancer. Additionally, Tiam1 depletion by RNAi in cervical cancer cells significantly decreased cell proliferation, migration and angiogenesis. In conclusion, our study demonstrated that upregulation of Tiam1 contributes to cervical cancer disease progression and indicates poor survival outcome.
T 淋巴瘤侵袭转移因子 1（Tiam1）是一种鸟嘌呤核苷酸交换因子，参与多种恶性肿瘤的发生。本研究旨在探讨 Tiam1 在宫颈癌进展中的作用，并评估其预后价值。采用免疫组织化学（IHC）染色法检测 174 例宫颈癌组织、92 例 CIN（宫颈上皮内瘤变）和 32 例正常宫颈上皮组织中 Tiam1 蛋白的表达水平。收集并比较不同 Tiam1 状态下的临床病理参数和总生存数据。采用 siRNA（小干扰 RNA）转染检测 Tiam1 在宫颈癌增殖、迁移和血管生成中的作用。结果显示，Tiam1 蛋白在宫颈癌组织中呈细胞质和核染色模式。在宫颈癌组织中，Tiam1 蛋白强阳性表达率为 51.72%（90/174），明显高于 CIN 组织和正常宫颈上皮组织（9.38%，3/32）。Tiam1 蛋白高表达与宫颈癌临床分期较晚、分化差、淋巴结（LN）转移、HPV 感染和总生存率（OS）降低密切相关。多因素分析表明，Tiam1 是宫颈癌患者的独立预后因素，与临床分期有关。此外，RNAi 沉默宫颈癌细胞中的 Tiam1 可显著降低细胞增殖、迁移和血管生成。综上所述，本研究表明 Tiam1 的上调促进了宫颈癌的疾病进展，并提示预后不良。
