Upregulation of Tiam1 contributes to cervical cancer disease progression and indicates poor survival outcome.

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.

High expression of NQO1 is associated with poor prognosis in serous ovarian carcinoma.

NAD(P)H: quinone oxidoreductase (NQO1) is a flavoprotein that catalyzes two-electron reduction and detoxification of quinones and its derivatives. NQO1 catalyzes reactions that have a protective effect against redox cycling, oxidative stress and neoplasia. High expression of NQO1 is associated with many solid tumors including those affecting the colon, breast and pancreas; however, its role in the progression of ovarian carcinoma is largely undefined. This study aimed to investigate the clinicopathological significance of high NQO1 expression in serous ovarian carcinoma. METHODS: NQO1 protein expression was assessed using immunohistochemical (IHC) staining in 160 patients with serous ovarian carcinoma, 62 patients with ovarian borderline tumors and 53 patients with benign ovarian tumors. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect NQO1 mRNA expression levels. The correlation between high NQO1 expression and clinicopathological features of ovarian carcinoma was evaluated by Chi-square and Fisher's exact test. Overall survival (OS) rates of all of ovarian carcinoma patients were calculated using the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazards regression model. RESULTS: NQO1 protein expression in ovarian carcinoma cells was predominantly cytoplasmic. Strong, positive expression of NQO1 protein was observed in 63.8% (102/160) of ovarian carcinomas, which was significantly higher than in borderline serous tumors (32.3%, 20/62) or benign serous tumors (11.3%, 6/53). Importantly, the rate of strong, positive NQO1 expression in borderline serous tumors was also higher than in benign serous tumors. High expression of NQO1 protein was closely associated with higher histological grade, advanced clinical stage and lower OS rates in ovarian carcinomas. Moreover, multivariate analysis indicated that NQO1 was a significant independent prognostic factor, in addition to clinical stage, in patients with ovarian carcinoma. CONCLUSIONS: NQO1 is frequently upregulated in ovarian carcinoma. High expressin of NQO1 protein may be an effective biomarker for poor prognostic evaluation of patients with serous ovarian carcinomas.