scholarly journals CCL2 is associated with metastasis and poor prognosis of bladder cancer

2019 ◽  
Author(s):  
wei gao ◽  
qiwang zhang ◽  
lianhua zhang ◽  
qiang liu ◽  
xuehui duan ◽  
...  

Abstract Background: Chemokine (C-C motif) ligand 2 (CCL2) is an important immune factor, which may be important in cancer progression by promoting proliferation, invasion metastasis and the tumor microenvironment. Recent researches have demonstrated that overexpression of CCL2 is associated with unfavorable prognosis in various cancer types. In this study, we aim to determine the prognostic value of CCL2 expression in patients with bladder cancer (BC). Methods: We retrospectively enrolled 154 patients with bladder cancer at Renji Hospital, Shanghai Jiaotong University between 2005 and 2007. CCL2 expression was assessed by immunohistochemical staining and its association with clinicopathologic features and prognosis were evaluated. Kaplan-Meier method was applied to compare survival curves. Cox regression models were fitted to analyze the effect of prognostic factors on Overall survival (OS). Results: CCL2 protein had high expression in 73 of 154 cases of BC (47%). CCL2 overexpression was significantly associated with tumor grade (P<0.001), stage (P=0.005), and lymph node metastasis (P=0.025). The Kaplan–Meier survival analysis demonstrated that CCL2 expression was significantly associated with DSS and OS (both P< 0.001). Multivariate analysis further demonstrated that CCL2 was an independent prognostic factor for patients with BC. Conclusion: CCL2 might be a new molecular marker to predict the prognosis of patients with BC. The novel risk classification based on combining CCL2 and TNM is more reliable than using either alone.

Author(s):  
M. P. Smal ◽  
N. V. Nikitchenko ◽  
A. I. Rolevich ◽  
T. I. Nabebina ◽  
S. A. Krasny ◽  
...  

To accurately predict the tumor behavior and individualize the treatment approach, new methods for bladder cancer (BC) prognosis are required. The most promising prognostic markers are the mutational and epigenetic changes of genes involved in maintaining cellular homeostasis. In the present study, we evaluated the influence of p16 promoter hypermethylation on the risk of recurrence, progression and disease outcome in the group of 158 BC patients. p16 epigenetic changes were found in 11.4 % of urothelial carcinomas and did not depend on clinicоmorphological characteristics. However, in the subgroup of patients with non-muscle invasive tumors, p16 abnormal methylation was significantly associated with smoking, and in the subgroup of patients with muscle-invasive BC, it was linked to a high tumor grade (G3). In the multivariate Cox regression analysis, p16 promoter hypermethylation was an independent predictor for bladder cancer progression (HR 6.84; 95 % CI 1.6–29.9; р = 0.011). The use of the data on the p16 methylation status may improve the accuracy of prognosis of the bladder cancer clinical course and the selection of appropriate treatment strategy.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1448
Author(s):  
Raquel Herranz ◽  
Julia Oto ◽  
Emma Plana ◽  
Álvaro Fernández-Pardo ◽  
Fernando Cana ◽  
...  

Bladder cancer (BC) is among the most frequent cancer types in the world and is the most lethal urological malignancy. Presently, diagnostic and follow-up methods for BC are expensive and invasive. Thus, the identification of novel predictive biomarkers for diagnosis, progression, and prognosis of BC is of paramount importance. To date, several studies have evidenced that cell-free DNA (cfDNA) found in liquid biopsies such as blood and urine may play a role in the particular scenario of urologic tumors, and its analysis may improve BC diagnosis report about cancer progression or even evaluate the effectiveness of a specific treatment or anticipate whether a treatment would be useful for a specific patient depending on the tumor characteristics. In the present review, we have summarized the up-to-date studies evaluating the value of cfDNA as potential diagnostic, prognostic, or monitoring biomarker for BC in several biofluids.


2020 ◽  
Author(s):  
Shuangqing Cao ◽  
Lei Zheng

Abstract Background: Present study was to investigate the relative expression and prognostic performance of protein phosphatase magnesium/manganese-dependent 1D (PPM1D) in bladder cancer.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) assay was performed to examine the relative expression of PPM1D mRNA in bladder cancer tissues and adjacent normal bladder tissues. The associations of PPM1D mRNA expression with clinicopathological features and the prognostic value were statistically analyzed via Chi-square test, Kaplan-Meier method and Cox regression analysis.Results: In comparison to adjacent normal tissues, PPM1D mRNA expression was obviously increased in bladder cancer tissues (P<0.001). Abnormal PPM1D expression was remarkably related to histological grade (P=0.017), TNM stage (P=0.032) and lymph nodes metastasis (P=0.035). Kaplan-Meier method showed that a close relationship was found between PPM1D expression and overall survival time (P=0.000). Multivariate analysis indicated that PPM1D expression (P=0.000, HR=3.530, 95%CI: 2.001-6.228) was a promising independent predictor for the prognosis of bladder cancer patients, as well as TNM stage (P=0.042, HR=1.768, 95%CI: 1.021-3.062).Conclusion: Taken together, our data showed that the potential performance of PPM1D as a prognostic biomarker and therapeutic target of bladder cancer.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4618-4618
Author(s):  
L. Yan ◽  
Y. Hu ◽  
M. R. D’Andrea ◽  
M. A. Towers ◽  
Y. Wang ◽  
...  

4618 Background: CCL2 (MCP-1) is a chemoattractant protein highly expressed in a variety of cancer types. The expression level of CCL2 has been linked to aggressive disease progression, early dissemination, and poor survival in certain cancers. Therefore, we assessed the potential association between CCL2 expression and patient prognosis in pancreatic cancer. Methods: Cylindrical tissue cores from a large retrospective, nonrandomized series covering 133 patients with resected pancreatic cancer were used to build a tissue microarray. CCL2 expression was determined using immunohistochemistry. Results: High intratumoral CCL2 expression and low intratumoral CCL2 expression were present in 44 (33%) and 89 (67%) tumors, respectively. Kaplan-Meier median survival among patients with low intratumoral CCL2 expression (19.1 months) was longer than that among those with high CCL2 expression (12.1 months). In multivariate analysis, more advanced pathological stage [risk ratio (RR) = 1.57; P = 0.038], poorly differentiated histology (RR = 1.68; P = 0.019), and high CCL2 expression [RR = 1.62; 95% confidence interval (CI) = 1.05–2.49; P = 0.028] were independent predictors of mortality. Conclusions: High CCL2 expression is a marker of poor prognosis in resected pancreatic cancer. [Table: see text]


2021 ◽  
Author(s):  
Deirdre De Ranieri ◽  
Angela Chun ◽  
Lutfiyya Muhammad

Abstract Background There are many FDA-approved corticosteroid preparations available for intra-articular injection, however triamcinolone hexacetonide is not one of them. It was the intraarticular drug of choice among pediatric rheumatologists up until approximately a decade ago, when production of this medication ceased. It can be obtained in the United States and Canada via importation from Europe, but it is not FDA-approved at this time. We wish to compare the duration of remission of intraarticular triamcinolone hexacetonide (TH) with that of triamcinolone acetonide (TA) in children with Juvenile Idiopathic Arthritis (JIA) and demonstrate its safety in this population. Methods This retrospective chart review included 39 patients with JIA who received intraarticular corticosteroid injections (IACIs) from September 2018 to September 2019. These patients were reviewed and their life-time injections with either TH (41 joints) or TA (124 joints) was noted through May 30, 2021. Patients with concomitant systemic therapy initiation were excluded. The primary outcome was time to relapse. Relapse was defined by the presence of arthritis on physical examination by an attending rheumatologist. Kaplan-Meier curves and a log-rank test were constructed to compare the probability of time to relapse between IACI injections. Additionally, mixed effects cox regression models were constructed to account for multiple injections per participant. Results Kaplan-Meier estimator of median relapse time in months was higher for TH. Based on the log-rank test, TA joints had a higher probability of experiencing a relapse during the study time (p-value < 0.001). The hazard of time to relapse was reduced when comparing TH to TA in both unadjusted and adjusted mixed effects cox regression models (unadjusted hazard ratio (95% confidence interval): 0.184 (0.089, 0.381); adjusted hazard ratio (95% confidence interval): 0.189 (0.092, 0.386)). Conclusions TH has longer duration of action than TA and is associated with less systemic side effects. It should be considered the drug of choice for intraarticular corticosteroid injections in children with JIA.


Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5931
Author(s):  
Shiv Verma ◽  
Eswar Shankar ◽  
Spencer Lin ◽  
Vaibhav Singh ◽  
E. Ricky Chan ◽  
...  

Bladder cancer prognosis remains dismal due to lack of appropriate biomarkers that can predict its progression. The study aims to identify novel prognostic biomarkers associated with the progression of bladder cancer by utilizing three Gene Expression Omnibus (GEO) datasets to screen differentially expressed genes (DEGs). A total of 1516 DEGs were identified between non-muscle invasive and muscle invasive bladder cancer specimens. To identify genes of prognostic value, we performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A total of seven genes, including CDKN2A, CDC20, CTSV, FOXM1, MAGEA6, KRT23, and S100A9 were confirmed with strong prognostic values in bladder cancer and validated by qRT-PCR conducted in various human bladder cancer cells representing stage-specific disease progression. ULCAN, human protein atlas and The Cancer Genome Atlas datasets were used to confirm the predictive value of these genes in bladder cancer progression. Moreover, Kaplan–Meier analysis and Cox hazard ratio analysis were performed to determine the prognostic role of these genes. Univariate analysis performed on a validation set identified a 3-panel gene set viz. CDKN2A, CTSV and FOXM1 with 95.5% sensitivity and 100% specificity in predicting bladder cancer progression. In summary, our study screened and confirmed a 3-panel biomarker that could accurately predict the progression and prognosis of bladder cancer.


Author(s):  
Nishant Sahni ◽  
Umesh Sharma ◽  
Rashi Arora

Background: Rising NT-proBNP are associated with reduced survival patients with HFrEF. However, it remains to be conclusively and formally demonstrated that the temporal trend in NT-proBNP level carries prognostic significance in HFpEF. Objective: To determine whether there is an association between rising NT-proBNP levels and 6-month survival in patients with HFpEF and HFrEF. Methods: We examined a cohort of 5203 patients to 5 hospitals in a regional health care system — who had at least one admission to the hospital with diagnoses of heart failure over a 3-year period. Kaplan-Meier survival curves were constructed for patients with downtrending (>25% net decrease), stable or uptrending (>25% net increase) NT-proBNP levels in HF, HFpEF and HFrEF patients. The log-rank test was used to test for differences in 6-month survival amongst the groups. Multivariate extended Cox regression models were constructed for 6-month survival with NT-proBNP as a time-varying covariate. Age, albumin, sex, race, serum creatinine, systolic and diastolic blood pressures and Charlson comorbidity scores at baseline were used as covariates in the model. Separate analyses were done for HFpEF and HFrEF patients. Results: HFpEF and HFrEF patients with up-trending levels had significantly lower 6-month survival rates than patients with downtrending or stable NT-proBNP levels. A doubling of the NT-proBNP level in patients was significantly associated with reduced 6-month survival in patients with in both subgroups of HF, HFpEF and HFrEF (HFpEF-HR: 1.53(1.49-2.57), HFrEF HR: 1.45(1.43-1.48) after adjusting for covariates.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xingyu Chen ◽  
Haotian Chen ◽  
Dong He ◽  
Yaxin Cheng ◽  
Yuxing Zhu ◽  
...  

The tumor microenvironment (TME) plays a crucial role in cancer progression and recent evidence has clarified its clinical significance in predicting outcomes and efficacy. However, there are no studies on the systematic analysis of TME characteristics in bladder cancer. In this study, we comprehensively evaluated the TME invasion pattern of bladder cancer in 1,889 patients, defined three different TME phenotypes, and found that different subtypes were associated with the clinical prognosis and pathological characteristics of bladder cancer. We further explored the signaling pathways, cancer-immunity cycle, copy number, and somatic mutation differences among the different subtypes and used the principal component analysis algorithm to calculate the immune cell (IC) score, a tool for comprehensive evaluation of TME. Univariate and multivariate Cox regression analyses showed that ICscore is a reliable and independent prognostic biomarker. In addition, the use of anti-programmed death-ligand (PD-L1) treatment cohort, receiver operating characteristic (ROC) curve, Tumor Immune Dysfunction and Exclusion (TIDE), Subnetwork Mappings in Alignment of Pathways (SubMAP), and other algorithms confirmed that ICscore is a reliable prognostic biomarker for immune checkpoint inhibitor response. Patients with higher ICscore showed a significant therapeutic advantage in immunotherapy. In conclusion, this study improves our understanding of the characteristics of TME infiltration in bladder cancer and provides guidance for more effective personalized immunotherapy strategies.


Author(s):  
Hamed Fouladseresht ◽  
Shahram Bolandparvaz ◽  
Hamid Reza Abbasi ◽  
Hossein Abdolrahimzadeh Fard ◽  
Shahram Paydar

The elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor clinical outcomes, especially in pro-inflammatory states such as surgical injuries and severe hemorrhages. Therefore, it was hypothesized whether NLR value at the time of admission could be a prognostic indicator of hospital mortality in trauma patients. This retrospective cohort study was conducted on 865 trauma patients referred to Rajaee Hospital between April 2016 and July 2019. The NLR value was calculated at the time of admission, and receiver operating characteristics (ROC) curve analysis was used to determine the cut-off point value of admission NLR related to hospital mortality of trauma patients. Furthermore, Kaplan-Meier survival analysis and Cox regression models have been applied to determine the effectiveness and prognostic potential of the admission NLR in the hospital mortality of trauma patients. The median age of the trauma patients was 32 years with an interquartile range (IQR) of 23 to 48 years, and most of them were male (83.9%). Also, trauma patients had a median injury severity score (ISS) of 9 (IQR=4-16) and a median Glasgow coma scale (GCS) of 14 (IQR=9-15). The cut-off value for admission NLR was 5.27 (area under the curve: 0.642, 95%CI: 0.559-0.726, p=0.001). In Kaplan-Meier survival analysis, the admission NLR>5.27 was an indicator of hospital mortality in trauma patients (p=0.001). Multivariate Cox regression models demonstrated that trauma patients with an admission NLR>5.27 had a 2.33-fold risk of hospital mortality (hazard ratio=2.33, 95%CI: 1.02-5.38, p=0.041). Furthermore, the admission NLR>5.27 was associated with a higher risk of hospital mortality in trauma patients with age≥65 years, systolic blood pressure≤90 mmHg, blood potassium>4.5 mmol/L, blood sodium>144 mEq/L, blood potential hydrogen (pH)≤7.28, GCS≤8, ISS>24 and blood base excess≤-6.1 mEq/L. The NLR value greater than 5.27 at the time of admission was associated with poorer outcomes, and it can be considered an independent prognostic indicator of hospital mortality in trauma patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Huiyuan Xiao ◽  
Wen Huang ◽  
Yanlei Li ◽  
Rongxin Zhang ◽  
Long Yang

Background: To explore the biological and clinical effects of titin-antisense RNA1 (TTN-AS1) in bladder cancer (BC) and the association between TTN-AS1 and activating transcription factor 2 (ATF2) in BC.Methods: The Kaplan–Meier method was performed to analyze the association between the expression of TTN-AS1 and prognosis of BC patients from TCGA data set and our institution. Quantitative real-time PCR (RT-PCR) was conducted to explore the expression of TTN-AS1 between the patients who underwent TURBT and Re-TURBT. MTT, colony formation, and tumor formation assays were conducted to evaluate the effect of TTN-AS1 on the ability of proliferation in BC cell lines. Transwell assay was performed to evaluate the effect of TTN-AS1 on the ability of invasion in BC cell lines. Bioinfomatics and immunohistochemical staining was used to identify the relationship between TTN-AS1 and ATF2.Results: The higher expression of TTN-AS1 was related to poorer disease-free survival (DFS) in patients with BC. The expression of TTN-AS1 was higher in BC patients who underwent Re-TURBT compared with BC patients who underwent TURBT. Knocking down TTN-AS1 resulted in inhibiting the ability of proliferation and invasion of BC cells. ATF2 may serve as a downstream target of TTN-AS1 in BC, and the high expression of ATF2 is also related to adverse DFS.Conclusion: Our study reveals that TTN-AS1 serves as an oncogene by activating ATF2 in BC. The findings suggest that TTN-AS1 may act as a novel therapeutic target for patients with BC.


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