Loss of Heterozygosis on IFN-α Locus is a Prognostic Indicator of Bacillus Calmette-Guerin Response for Nonmuscle Invasive Bladder Cancer

Cai, Tommaso; Nesi, Gabriella; Canto, Maurizio Dal; Tinacci, Galliano; Mondaini, Nicola; Piazzini, M; Geppetti, Pierangelo; Bartoletti, Riccardo

doi:10.1016/j.juro.2009.12.105

Cited by 14 publications

(14 citation statements)

References 22 publications

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“…Clinical data indicate that chromosome 9p21 deletions occurred preferentially in larger tumors (>5 cm diameter). Another study has also reported that LOH on IFN-alpha locus at 9p21 is a prognostic indicator of bacillus Calmette-Guerin response for non-muscle invasive bladder cancer [46]. Similarly, Roman et al [47] has investigated the chromosomal aberrations in head and neck squamous cell carcinomas by array CGH and found that the genes involved in cytokine-cytokine receptor interaction pathway were the largest group of genes (23/149) showing chromosomal gains.…”

Section: Discussionmentioning

confidence: 94%

A Meta-Analysis of Array-CGH Studies Implicates Antiviral Immunity Pathways in the Development of Hepatocellular Carcinoma

Guo

Yanna

et al. 2011

PLoS ONE

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BackgroundThe development and progression of hepatocellular carcinoma (HCC) is significantly correlated to the accumulation of genomic alterations. Array-based comparative genomic hybridization (array CGH) has been applied to a wide range of tumors including HCCs for the genome-wide high resolution screening of DNA copy number changes. However, the relevant chromosomal variations that play a central role in the development of HCC still are not fully elucidated.MethodsIn present study, in order to further characterize the copy number alterations (CNAs) important to HCC development, we conducted a meta-analysis of four published independent array-CGH datasets including total 159 samples.ResultsEighty five significant gains (frequency ≥25%) were mostly mapped to five broad chromosomal regions including 1q, 6p, 8q, 17q and 20p, as well as two narrow regions 5p15.33 and 9q34.2-34.3. Eighty eight significant losses (frequency ≥25%) were most frequently present in 4q, 6q, 8p, 9p, 13q, 14q, 16q, and 17p. Significant correlations existed between chromosomal aberrations either located on the same chromosome or the different chromosomes. HCCs with different etiologies largely exhibited surprisingly similar profiles of chromosomal aberrations with only a few exceptions. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the genes affected by these chromosomal aberrations were significantly enriched in 31 canonical pathways with the highest enrichment observed for antiviral immunity pathways.ConclusionsTaken together, our findings provide novel and important clues for the implications of antiviral immunity-related gene pathways in the pathogenesis and progression of HCC.

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Section: Discussionmentioning

confidence: 94%

A Meta-Analysis of Array-CGH Studies Implicates Antiviral Immunity Pathways in the Development of Hepatocellular Carcinoma

Guo

Yanna

et al. 2011

PLoS ONE

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“…To our knowledge, only one study has been reported and evaluated the role of loss of heterozygosity (LOH) in the IFN-a (chromosome 9p21) to predict BCG response in patients who underwent TURBT. Results showed that LOH at the IFN-a locus was an independent predictor of BCG response ( p = 0.002) and was significantly associated with increased BCG failure ( p < 0.0001) [7]. …”

Section: Evidence Synthesismentioning

confidence: 99%

“…These alterations included single-nucleotide polymorphisms (SNPs), single-nucleotide variations (SNVs), and mutations [5, 6]. Second, various genetic copy number alterations were associated with bladder cancer [7]. Third, epigenetic regulation of genes, especially by gene methylation, was found to be associated with BCG failure for multiple genes [8–10].…”

Section: Introductionmentioning

confidence: 99%

Prediction of Bacillus Calmette-Guerin Response in Patients with Bladder Cancer after Transurethral Resection of Bladder Tumor by Using Genetic Variation Based on Genomic Studies

Zhang

Jiang

Liu

et al. 2016

BioMed Research International

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Purpose. We aimed to comprehensively review contemporary literature on genetic and epigenetic biomarkers associated with the prediction of Bacillus Calmette-Guerin (BCG) response after the transurethral resection of a bladder tumor and to discuss the application of these biomarkers in precision cancer care for bladder cancer. Method. We performed a systematic review of published literatures in the databases PubMed and Embase by using the following key words: bladder cancer, BCG, gene, and methylation. Studies associated with cell lines, animal models, and muscle invasive bladder cancer were excluded. Results. The genetic variations associated with BCG response can be classified into three categories: germline variations, somatic variations, and epigenetic alterations. Genes related to BCG response were mainly involved in single-nucleotide polymorphisms, copy number variations, and gene methylations. Conclusions. Although these gene alterations are currently the most promising predictive markers of BCG response, most studies about bladder cancer DNA biomarkers are related to germline variations in candidate genes, and the results are not consistent. Only one study is related to somatic variation, and further evaluation in large-scale validation studies should be conducted to assess the potential clinical application of these findings. In addition, other biomarkers based on different “–omics” technologies should be considered in future studies.

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“…Chen et al demonstrated that BCG increases IL-6 messenger RNA and protein in a time-and dose-dependent manner via an immediate early pathway (12). Furthermore, we highlighted the feasible role of IL-6 and IL-10 ratio (IL-6/IL-10) as a prognostic marker of recurrence in patients affected by NMIBC (9). Urinary interleukins could consequently be used as prognosticators to better assess the outcome of NMIBC patients following BCG therapy.…”

Section: Introductionmentioning

confidence: 98%

“…Therefore, the patient failing BCG therapy is a challenge to the urologist and predictors of BCG response should be investigated (2). Although several authors have proposed molecular markers to predict the clinical outcome of patients with non-muscle invasive bladder cancer (NMIBC) following treatment with intravesical BCG (8–9), no marker has yet proven to be valid in everyday clinical practice (2). Zhang et al demonstrated the induction of cytokine production by BCG, particularly interleukin-6 (IL-6) (10).…”

Section: Introductionmentioning

confidence: 99%

Prediction of response to bacillus Calmette-Guérin treatment in non-muscle invasive bladder cancer patients through interleukin-6 and interleukin-10 ratio

Cai

Nesi

Mazzoli

et al. 2012

Experimental and Therapeutic Medicine

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This study aimed to evaluate whether the interleukin-6 (IL-6) and interleukin-10 (IL-10) ratio (IL-6/IL-10) can be used as a prognostic marker of recurrence following bacillus Calmette-Guérin (BCG) therapy in patients with high-risk non-muscle invasive bladder cancer (NMIBC). One hundred and twenty-one consecutive urological patients (72 affected by high-risk NMIBC and 49 controls) were selected for this prospective study. Urine samples for dipstick and interleukin analyses were collected from each subject before surgery. All patients underwent transurethral resection of bladder tumours (TUR-BT), followed by six weekly BCG instillations. IL-6 and IL-10 concentrations in urine were determined by solid phase ELISA Quantikine IL-6 and IL-10 Immunoassay. Patients with NMIBC were stratified in accordance with IL-6/IL-10: group A ≤0.09 and group B >0.10. The main outcome measures were time to first recurrence and recurrence rate following BCG therapy. At enrolment, IL-6/IL-10 was not statistically different between patients and controls (p=0.763, degrees of freedom (df)=1, F-test result (F)=0.092). Of the 72 patients with NMIBC, 38 (52.7%) had an IL-6/IL-10 of ≤0.09 (group A), while 34 (47.3%) had an IL-6/IL-10 of >0.10 (group B). A significant difference between IL-6/IL-10 and status at follow-up was found (p=0.016, df=1, χ2=5.800). The Kaplan-Meier curves demonstrated that group B patients had a significantly higher probability of being recurrence-free than group A patients [p=0.003; recurrence rate (RR)=3.1]. At multivariate analysis, IL-6/IL-10 (p<0.003) and the number of lesions (p<0.001) were identified as independent predictors of BCG response probability. In conclusion, this study highlights the feasible role of IL-6/IL-10 in predicting recurrence following BCG therapy in high-risk NMIBC.

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Loss of Heterozygosis on IFN-α Locus is a Prognostic Indicator of Bacillus Calmette-Guerin Response for Nonmuscle Invasive Bladder Cancer

Abstract: This study highlights the predictive value of loss of heterozygosity analysis on interferon-alpha in patients with nonmuscle invasive bladder cancer treated with bacillus Calmette-Guerin.

Cited by 14 publications

References 22 publications

A Meta-Analysis of Array-CGH Studies Implicates Antiviral Immunity Pathways in the Development of Hepatocellular Carcinoma

A Meta-Analysis of Array-CGH Studies Implicates Antiviral Immunity Pathways in the Development of Hepatocellular Carcinoma

Prediction of Bacillus Calmette-Guerin Response in Patients with Bladder Cancer after Transurethral Resection of Bladder Tumor by Using Genetic Variation Based on Genomic Studies

Prediction of response to bacillus Calmette-Guérin treatment in non-muscle invasive bladder cancer patients through interleukin-6 and interleukin-10 ratio

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