Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Input: Consider Input: MicroRNA-222 (miR-222) has been shown to play a potential oncogenic role in bladder cancer. The aim of this study was to evaluate the expression of miR-222 in bladder cancer and its potential relevance to clinicopathological characteristics and patient survival.', 'Surgical specimens of cancer tissue and adjacent normal tissue were obtained from 97 patients with bladder cancer. The relative expression levels of miR-222 in the cancer and the normal adjacent tissue were measured by quantitative reverse-transcriptase PCR. We analyzed their correlation with clinicopathological parameters and prognostic value.', 'The expression level of miR-222 was significantly higher in tumor tissues than in corresponding non-cancerous tissues (5.46\u2009±\u20091.45 versus 1.92\u2009±\u20090.65, P\u2009< \u20090.0001), and a high expression of miR-222 was found to be significantly associated with tumor grade (P\u2009=\u20090.003) and tumor stage (P\u2009=\u20090.005). The miR-222 expression level was classified as high or low in relation to the median value (cutoff value\u2009=\u20095.15). Kaplan-Meier analysis showed that patients with higher levels of miR-222 had significantly poorer survival than those with lower expression of this miRNA in patients, with a 5-year overall survival of 29.53% and 52.75%, respectively (P\u2009=\u20090.0034). In the multivariate Cox proportional hazards analysis, which included miR-222 level, tumor grade, tumor stage, and tumor number, high miR-222 expression was independently associated with poor survival (P\u2009<\u20090.001; hazard ratio 6.17; 95% CI 2.33 to 10.39).

Output: Is increased expression of miR-222 associated with poor prognosis in bladder cancer?


Input: Consider Input: Wnt proteins are important for developmental processes and certain diseases. WNT5A is a non-canonical Wnt protein that previously has been shown to play a role in the progression of malignant melanoma. High expression of WNT5A in melanoma tumors correlates to formation of distant metastasis and poor prognosis. This has partly been described by the findings that WNT5A expression in melanoma cell lines increases migration and invasion.', 'Malignant melanoma cell lines were treated with rWNT5A or WNT5A siRNA, and mRNA versus protein levels of soluble mediators were measured using RT-PCR, cytokine bead array and ELISA. The induced signaling pathways were analyzed using inhibitors, Rho-GTPase pull down assays and western blot. Ultracentrifugation and electron microscopy was used to analyze microvesicles. Gene expression microarray data obtained from primary malignant melanomas was used to verify our data.', 'We show that WNT5A signaling induces a Ca2+-dependent release of exosomes containing the immunomodulatory and pro-angiogenic proteins IL-6, VEGF and MMP2 in melanoma cells. The process was independent of the transcriptional machinery and depletion of WNT5A reduced the levels of the exosome-derived proteins. The WNT5A induced exosomal secretion was neither affected by Tetanus toxin nor Brefeldin A, but was blocked by the calcium chelator Bapta, inhibited by a dominant negative version of the small Rho-GTPase Cdc42 and was accompanied by cytoskeletal reorganization. Co-cultures of melanoma/endothelial cells showed that depletion of WNT5A in melanoma cells decreased endothelial cell branching, while stimulation of endothelial cells with isolated rWNT5A-induced melanoma exosomes increased endothelial cell branching in vitro. Finally, gene expression data analysis of primary malignant melanomas revealed a correlation between WNT5A expression and the angiogenesis marker ESAM.

Output: Does wNT5A induce release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells?


Input: Consider Input: Hepatocellular carcinoma (HCC) is one of the most common solid tumors and ranks the third leading cause of cancer mortality worldwide. The purpose of this study was to examine the expression dynamics of GOLPH3 in HCC tissue samples, and explore the correlation between GOLPH3 expression and prognosis in patients with HCC.', 'The levels of Golgi phosphoprotein 3 (GOLPH3) mRNA and protein in liver cancer cell lines and fresh tissues were determined by qRT-PCR and Western blotting. Additionally, the protein expression of GOLPH3 was detected by immunohistochemistry.', 'High GOLPH3 expression was positively correlated with serum AFP level (P=0.015) and tumor recurrence or metastasis (P=0.010). In addition, liver cancer patients with high GOLPH3 expression had significantly poorer overall survival (HR, 1.87; 95% CI, 1.19-2.94; P=0.006) and poorer disease-free survival (HR, 1.90; 95% CI, 1.21-2.98; P=0.005) than those with low GOLPH3 expression. The cumulative 5-year survival rate was only 35.19% (95% CI, 26.18%-44.20%) in the high GOLPH3 expression group, whereas it was 55.93% (95% CI, 43.26%-68.60%) in the low GOLPH3 expression group. Furthermore, multivariate Cox regression analysis demonstrated that the expression of GOLPH3, tumor size and tumor multiplicity were independent prognostic predictors for HCC patients.


Output: Is gOLP3 a predictor of survival in patients with hepatocellular carcinoma?