The prognostic effect of metastasis patterns on overall survival in patients with distant metastatic bladder cancer: a SEER population-based analysis.

BACKGROUND: The prognostic impact of different distant metastases pattern in bladder cancer is unexplored still now. The aim of this study is to investigate the impact of different distant metastases pattern on the survival of patients with stage IV bladder cancers. METHODS: A SEER analysis was performed and the overall survival was calculated by the Kaplan-Meier method. Multivariable Cox regression models were used to further analyze survival outcome and other prognostic factors. RESULTS: A total of 90,382 eligible cases were retrieved in the Surveillance, Epidemiology, and End Results database. Among these patients, stage of IV bladder cancer accounted for 7.03% (6354/90382) at initial diagnosis. Patients who suffered metastasis occupied 35.51% (2256/6354). Comparing with other three single metastases, the patients with liver metastasis exhibited worst OS whose mean of survival was 7.118 months. Multivariate analysis with Cox hazard regression model showed that metastatic site was an independent prognostic factor of OS in patients with single metastasis (P < 0.05). The results of univariate survival analysis showed that metastatic pattern, sex, age, race, tumor stage, N-classification, differentiated grade, histological type, chemotherapy, radiotherapy and insurance status were not significantly correlated with overall survival of patients with two or three metastatic sites (all, P > 0.05). CONCLUSIONS: Bone was the most common site of single metastasis for bladder cancers. Patients with liver metastasis had worse survival outcome comparing with other three distant metastases. Knowledge of these differences in metastatic patterns might help to better guide pre-treatment evaluation of bladder cancer and make determination regarding curative-intent interventions.

Overexpression of Citron Rho-Interacting Serine/Threonine Kinase Associated with Poor Outcome in Bladder Cancer.

Objective: Citron Rho-Interacting Serine/Threonine Kinase (CIT) was originally identified as a binding partner of active forms of the small GTPases Rho and Rac. This kinase participated in the regulation of cytokinesis and loss of CIT was associated with chromosomal instability. Here, we assume that CIT might be a potential prognostic biomarker for bladder cancer. Materials and Methods: The expression and prognostic significance of CIT mRNA were validated on 5 published microarray data sets, including 948 bladder cancer cases. To further confirm the results, we collected 54 non-carcinomatous human bladder tissue samples and 315 bladder cancer tissues from Zhejiang Provincial People's Hospital to detect the protein level of CIT based on the immunohistochemistry analysis. The Kaplan-Meier method and Cox proportional hazards regression model were used in survival analysis. Results: Analysis results showed that high CIT expression was associated with tumor size (p=0.0001), tumor grade (p<0.0001), smoking status (p=0.0143), TNM stage (p=0.0024), pathological tumor stage (p<0.0001) and aggressive phenotypes of bladder cancer. Independent and pooled survival analyses both indicated that overexpression of CIT was significantly associated with poor survival of bladder cancers. Conclusions: In conclusion, these findings indicated that overexpression of CIT was significantly associated with poor survival outcome in bladder cancers. CIT might serve as a promising prognostic biomarker and therapeutic target for bladder cancers.

Long noncoding RNA SOX2-OT facilitates prostate cancer cell proliferation and migration via miR-369-3p/CFL2 axis.

Accepted as crucial participators in human malignancies, long noncoding RNAs (lncRNAs) have been proven to exert significant function on the complicated processes of cancer progression. Although existing investigations have revealed the oncogenic role of lncRNA SOX2 overlapping transcript (SOX2-OT) in different kinds of cancers, such as osteosarcoma and cholangiocarcinoma, the potential role of it in prostate cancer (PC) is poorly understood. This study was the first attempt to decipher the underlying regulatory mechanism of SOX2-OT in PC. According to the data from this study, SOX2-OT expression was conspicuously elevated in PC tissues and cells. Silenced SOX2-OT could repress PC cell proliferation and migration. Besides, mechanism assays manifested that SOX2-OT bound with miR-369-3p and negatively correlated with miR-369-3p in PC. Additionally, miR-369-3p was confirmed to elicit suppressive impact on PC progression. What's more, cofilin 2 (CFL2) was testified to be a downstream target gene of miR-369-3p. Final rescue tests uncovered that CFL2 upregulation or miR-369-3p inhibition could largely restore SOX2-OT knockdown-mediated function on PC progression. To sum up, SOX2-OT accelerates cell proliferation and migration by targeting miR-369-3p/CFL2 axis in PC.

The prognosis of different distant metastases pattern in prostate cancer: A population based retrospective study.

BACKGROUND: The present of metastases is a poor prognostic factor in prostate cancer, but the prognostic impact of different distant metastases pattern is unclear. The aim of this study is to investigate the impact of different distant metastases pattern on the survival of patients with stage IV prostate cancer. METHODS: Data queried for this study include prostate cancer (2010-2014) from the Surveillance, Epidemiology, and End Results (SEER) program. Metastatic distribution information was provided for bone, brain, liver and lung. The overall survival was calculated by the Kaplan-Meier method. Multivariable Cox regression models were used to analyze survival outcome and risk factors. RESULTS: A total of 265 900 eligible patients were identified from SEER database. Among these patients, stage of IV prostate cancer accounted for 7.53% (20 034/265 900) at diagnosis. Patients who suffered metastasis to either one of the four organs occupied 61.24% (12 268/20 034) in stage of IV patients. Comparing with other three single metastases, the patients with liver metastasis exhibited worst OS whose mean survival was 17.529 months (P < 0.001). The mean survival of metastases with bong and lung was 25.238 months, which was the best survival of the six forms with two metastatic sites (P < 0.001). The results of univariate survival analysis showed that metastatic forms, race, N-classification and differentiated grade did not have impact on the overall survival of patients with three metastatic sites (all, P > 0.05). CONCLUSIONS: In analysis of both one and two metastatic sites, patients with liver metastasis seemed to have worse survival outcome. On the other hand, bone metastasis had better outcome than other three visceral metastases. Knowledge of these differences in metastatic patterns may help to better guide pre-treatment evaluation of prostate cancer and make determination regarding curative-intent interventions.

Treatment and survival outcomes of lobular carcinoma in situ of the breast: a SEER population based study.

Lobular carcinoma in situ (LCIS) represents 5.3% of in situ specimens, and is thought to carry a low risk for developing to the invasive lobular breast cancer (ILC). There is still no standard care approach for patients with LCIS. We aimed to define the impacts of surgical and radiation intervention on survival outcomes of LCIS. LCIS cases from 2004 to 2013 of the recent Surveillance, Epidemiology, and End Results (SEER) database were analyzed. Clinicopathologic features were analyzed in 16002 patients between 2004 and 2013. Treatment modalities included no surgery (NS), lumpectomy alone (LA), lumpectomy with radiation treatment (LRT), mastectomy alone (MA) and mastectomy with radiation treatment (MRT). The overall survival (OS) was calculated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using the variables of treatment, race, hormone receptor status, grade and age. Among 16002 patients, median follow-up was 54 months. Patients treated with LA had superior OS for NS (P = 0.001), MA (P < 0.001) and MRT P = 0.018). LRT only had superior OS for MRT (P = 0.009). There was no statistically significance between LA and LRT (P = 0.317). Improved OS was also correlated with younger age (P < 0.001), progesterone receptor positive (P = 0.001). Black patients had the worst OS (P < 0.001). There was no obvious survival difference among grade groups (P = 0.536). The LCIS patients treated with LA or LRT had better survival comparing with other groups. Considering the medical expense and the risk of radiotherapy, LA may be the most appropriate therapy for patients with LCIS.

Worse outcome in breast cancer with higher tumor-infiltrating FOXP3+ Tregs : a systematic review and meta-analysis.

BACKGROUND: Forkhead box P3(FOXP3) is known as the optimum maker for regulatory T cells(Tregs), which are conventionally thought to induce immune tolerance to disturb the antitumor immunity. However, the research on the prognostic significance of tumor-infiltrating FOXP3+ Tregs in breast cancer is still limited and the results are controversial. METHODS: We searched for studies in PubMed, EMBASE and Web of Science prior to January 2015. The correlation between FOXP3+ tumor-infiltrating lymphocytes(TILs) and breast cancer prognosis was analyzed. The meta-analysis was performed using STATA 11.0. Pooled hazard ratios (HRs) with 95 % confidence intervals (CIs) were used to estimate the degree of the association between FOXP3+ TILs and prognosis of breast cancers, while relative ratios (RRs) were used to evaluate the relationship between FOXP3+ TILs and clinicopathological features of breast cancers. RESULT: A total of 15 studies comprising 8666 breast cancer patients met the inclusion criteria. Our results showed that higher FOXP3+ TILs level was significantly associated with poor prognosis in terms of overall survival (OS) (pooled HR:1.60, 95 % CI:1.06-2.42; P < 0.05). We found that breast cancer with higher FOXP3+ TILs level was positively correlated with c-erbB-2 positive status (pooled RR:1.52, 95 % CI:1.32-1.75; P < 0.05), lymph node positive status(pooled RR:1.17, 95 % CI:1.04-1.32; P < 0.05) while there was a negative association with ER positive status(pooled RR:0.65, 95 % CI:0.56-0.76; P < 0.05) and PR positive status(pooled RR:0.66, 95 % CI:0.51-0.87; P < 0.05). CONCLUSION: The present results of meta-analysis showed that higher FOXP3+ TILs level in patients with breast cancer led to poor overall survival (OS) and was significantly associated with c-erbB-2 status, lymph node status, ER status and PR status. FOXP3+ TILs level is a promising prognostic factor in breast cancer.

Prognostic value of FOXA1 in breast cancer: A systematic review and meta-analysis.

BACKGROUND: Despite some published papers analyzing the prognostic role of forkhead-box A1 (FOXA1) in breast cancer, it has not yet been considered as an established prognostic factor in clinical practice. The present meta-analysis evaluated the prognostic value of FOXA1 in breast cancer. METHODS: PubMed, Web of Science and Embase databases were searched for relevant published literature that evaluated the correlation between FOXA1 and breast cancer. Either a fixed or random effect model was applied to estimate the pooled hazard ratio (HR) for FOXA1 prognosis in breast cancer. RESULT: A total of nine articles comprising 6386 breast cancer patients met the inclusion criteria. Among these nine studies, five studies and four studies investigated the prognostic association with disease-free survival (DFS), and overall survival (OS), respectively. Meta-analysis results suggested that high FOXA1 expression was positively associated with DFS (pooled HR: 0.43, 95% CI: 0.23-0.81; P < 0.05) and OS (pooled HR: 0.39, 95% CI: 0.26-0.60; P < 0.05) in breast cancer patients. No publication bias was discovered by Begg's test in this meta-analysis. CONCLUSION: The results from this meta-analysis indicated that elevated FOXA1 expression level was associated with better outcome in breast cancer.

Butylated hydroxyanisole induces distinct expression patterns of Nrf2 and detoxification enzymes in the liver and small intestine of C57BL/6 mice.

Butylated hydroxyanisole (BHA) is widely used as an antioxidant and preservative in food, food packaging and medicines. Its chemopreventive properties are attributing to its ability to activate the transcription factor NF-E2 p45-related factor 2 (Nrf2), which directs central genetic programs of detoxification and protection against oxidative stress. This study was to investigate the histological changes of Nrf2 and its regulated phase II enzymes Nqo1, AKR1B8, and Ho-1 in wild-type (WT) and Nrf2(-/-) mice induced by BHA. The mice were given a 200mg/kg oral dose of BHA daily for three days. Immunohistochemistry revealed that, in the liver from WT mice, BHA increased Nqo1 staining in hepatocytes, predominately in the pericentral region. In contrast, the induction of AKR1B8 appeared mostly in hepatocytes in the periportal region. The basal and inducible Ho-1 was located almost exclusively in Kupffer cells. In the small intestine from WT mice, the inducible expression patterns of Nqo1 and AKR1B8 were nearly identical to that of Nrf2, with more intense staining in the villus than that the crypt. Conversely, Keap1 was more highly expressed in the crypt, where the proliferative cells reside. Our study demonstrates that BHA elicited differential expression patterns of phase II-detoxifying enzymes in the liver and small intestine from WT but not Nrf2(-/-) mice, demonstrating a cell type specific response to BHA in vivo.

Differential expression patterns of Nqo1, AKR1B8 and Ho-1 in the liver and small intestine of C57BL/6 mice treated with sulforaphane.

This data article contains complementary figures and results related to the research article entitled "butylated hydroxyanisole induces distinct expression patterns of Nrf2 and detoxification enzymes in the liver and small intestine of C57BL/6 mice" (Luo et al., 2015 [1]), which defined the basal and butylated hydroxyanisole (BHA)-induced expression patterns of Phase II enzymes Nqo1, AKR1B8, and Ho-1 in the liver and small intestine of C57BL/6 mice. Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)butane] (SFN), a naturally occurring isothiocyanate derived from cruciferous vegetables, is a highly potent inducer of phase II cytoprotective enzymes. This dataset reports the histological changes of Nqo1, AKR1B8, and Ho-1 in wild-type (WT) and Nrf2 (-/-) mice induced by SFN. The mice were given a 25 mg/kg single oral dose of SFN for 24 h and 48 h. Immunohistochemistry revealed that, in the liver from WT mice, SFN increased Nqo1 staining in hepatocytes with slight higher staining in the pericentral region. The induction of AKR1B8 appeared mostly in hepatocytes in the periportal region. The basal and inducible Ho-1 was located predominately in Kupffer cells. In the small intestine from WT mice, the inducible expression of Nqo1 and AKR1B8 appeared more obvious in the villus than that in the crypt.